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J. Alan Diehl

TitleEndowed Chair, SmartState Endowed Chair in Lipidomics and Pathobiology
InstitutionMedical University of South Carolina
DepartmentBiochemistry and Molecular Biology
AddressP.O. Box MSC 509
712F
Hollings Cancer Center - 86 Jonathan Lucas St.
Phone843-792-1449
Fax843-792-8304
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    Collapse Overview 
    Collapse overview
    The Diehl lab focuses on the mechanisms whereby extra-cellular signals are sensed by the cell cycle machine and are then transmitted into regulated cell cycle progression. Elucidation of these mechanisms provides a framework wherein we can understand and interrogate growth regulatory pathways that are subverted during tumor development and progression. One major focus of the laboratory concerns the mechanisms whereby growth-signaling pathways regulate the mitogenically responsive D-type cyclins and more specifically, how these pathways regulate accumulation of an active, nuclear cyclin D1-dependent kinase. Our current work focuses on the role of E3 ubiquitin ligases in the maintenance of cyclin D1 levels and the physiological function of the E3 ligase in tumor suppression. Additional work focuses on the regulation of novel downstream substrates of the cyclin D1/CDK4 kinase and their role in mediating cyclin D1-dependent effects on tumor cell gene expression networks.

    A second area of interest concerns how a stress-induced signaling pathway emanating from the endoplasmic reticulum (ER) regulates cell cycle progression, lipid biosynthesis and cell survival during tumor progression. The initial rapid expansion of tumor cells can result in a microenvironment wherein metabolic nutrients such as glucose, oxygen, and growth factors become limited as cellular volume expands beyond the established vascularity of the tissue. The endoplasmic reticulum is acutely sensitive to limiting levels of glucose and oxygen and thus functions as an early “sensor” for these cellular nutrients. Mammalian cells contain three distinct ER transmembrane protein kinases (PERK, Ire1a, and Ire1ß) that function as proximal effectors that are activated upon nutrient deprivation. These protein kinases coordinate the induction of ER chaperones, suppress protein synthesis, inhibit cell cycle progression, and promote apoptotic cell death. The Diehl laboratory has previously demonstrated that PERK mediates UPR-induced cell cycle arrest via inhibition of cyclin D1 protein synthesis. PERK also contributes to cellular adaptation via activation of a gene expression program that is dependent upon anti-oxidant signaling and Akt activation. More recently, the Diehl laboratory has identified micro-RNAs that are responsive to ER stress. Elucidating the targets and biological significance of these miRNAs with regard to tumor progression is currently a major focus.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Rozpedek W, Pytel D, Poplawski T, Walczak A, Gradzik K, Wawrzynkiewicz A, Wojtczak R, Mucha B, Diehl JA, Majsterek I. Inhibition of the PERK-Dependent Unfolded Protein Response Signaling Pathway Involved in the Pathogenesis of Alzheimer's Disease. Curr Alzheimer Res. 2019; 16(3):209-218. PMID: 30819079.
      View in: PubMed
    2. Rozpedek W, Pytel D, Nowak-Zdunczyk A, Lewko D, Wojtczak R, Diehl JA, Majsterek I. Breaking the DNA damage response via serine/threonine kinase inhibitors to improve cancer treatment. Curr Med Chem. 2018 Jan 16. PMID: 29345572.
      View in: PubMed
    3. Hogaboom NS, Diehl JA, Oyster ML, Koontz AM, Boninger ML. Ultrasonographic Median Nerve Changes After Repeated Wheelchair Transfers in Persons With Paraplegia: Relationship With Subject Characteristics and Transfer Skills. PM R. 2016 Apr; 8(4):305-313. PMID: 26265431.
      View in: PubMed
    4. Goldhammer JE, Marhefka GD, Daskalakis C, Berguson MW, Bowen JE, Diehl JT, Sun J. The Effect of Aspirin on Bleeding and Transfusion in Contemporary Cardiac Surgery. PLoS One. 2015; 10(7):e0134670. PMID: 26230605.
      View in: PubMed
    5. Pytel D, Majsterek I, Diehl JA. Tumor progression and the different faces of the PERK kinase. Oncogene. 2016 Mar 10; 35(10):1207-15. PMID: 26028033.
      View in: PubMed
    6. Dey S, Sayers CM, Verginadis II, Lehman SL, Cheng Y, Cerniglia GJ, Tuttle SW, Feldman MD, Zhang PJ, Fuchs SY, Diehl JA, Koumenis C. ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. J Clin Invest. 2015 Jul 01; 125(7):2592-608. PMID: 26011642.
      View in: PubMed
    7. Augello MA, Berman-Booty LD, Carr R, Yoshida A, Dean JL, Schiewer MJ, Feng FY, Tomlins SA, Gao E, Koch WJ, Benovic JL, Diehl JA, Knudsen KE. Consequence of the tumor-associated conversion to cyclin D1b. EMBO Mol Med. 2015 May; 7(5):628-47. PMID: 25787974.
      View in: PubMed
    8. Qiu B, Ackerman D, Sanchez DJ, Li B, Ochocki JD, Grazioli A, Bobrovnikova-Marjon E, Diehl JA, Keith B, Simon MC. HIF2a-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma. Cancer Discov. 2015 Jun; 5(6):652-67. PMID: 25829424.
      View in: PubMed
    9. Kinugasa H, Whelan KA, Tanaka K, Natsuizaka M, Long A, Guo A, Chang S, Kagawa S, Srinivasan S, Guha M, Yamamoto K, St Clair DK, Avadhani NG, Diehl JA, Nakagawa H. Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression. Oncogene. 2015 Oct 08; 34(41):5229-39. PMID: 25659582.
      View in: PubMed
    10. Li Y, Chitnis N, Nakagawa H, Kita Y, Natsugoe S, Yang Y, Li Z, Wasik M, Klein-Szanto AJ, Rustgi AK, Diehl JA. PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers. Cancer Discov. 2015 Mar; 5(3):288-303. PMID: 25582697.
      View in: PubMed
    11. Lian Z, Lee EK, Bass AJ, Wong KK, Klein-Szanto AJ, Rustgi AK, Diehl JA. FBXO4 loss facilitates carcinogen induced papilloma development in mice. Cancer Biol Ther. 2015; 16(5):750-5. PMID: 25801820.
      View in: PubMed
    12. Rozpedek W, Markiewicz L, Diehl JA, Pytel D, Majsterek I. Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer's Disease. Curr Med Chem. 2015; 22(27):3169-84. PMID: 26282939.
      View in: PubMed
    13. Maas NL, Diehl JA. Molecular pathways: the PERKs and pitfalls of targeting the unfolded protein response in cancer. Clin Cancer Res. 2015 Feb 15; 21(4):675-9. PMID: 25182515.
      View in: PubMed
    14. Kagawa S, Natsuizaka M, Whelan KA, Facompre N, Naganuma S, Ohashi S, Kinugasa H, Egloff AM, Basu D, Gimotty PA, Klein-Szanto AJ, Bass AJ, Wong KK, Diehl JA, Rustgi AK, Nakagawa H. Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities. Oncogene. 2015 Apr 30; 34(18):2347-59. PMID: 24931169.
      View in: PubMed
    15. Maas NL, Singh N, Diehl JA. Generation and characterization of an analog-sensitive PERK allele. Cancer Biol Ther. 2014 Aug; 15(8):1106-11. PMID: 24846185.
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    16. Pytel D, Seyb K, Liu M, Ray SS, Concannon J, Huang M, Cuny GD, Diehl JA, Glicksman MA. Enzymatic Characterization of ER Stress-Dependent Kinase, PERK, and Development of a High-Throughput Assay for Identification of PERK Inhibitors. J Biomol Screen. 2014 Aug; 19(7):1024-34. PMID: 24598103.
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    17. Tanaka D, Unai S, Diehl JT, Hirose H. Surgical removal of a large mobile left ventricular thrombus via left atriotomy. World J Clin Cases. 2014 Feb 16; 2(2):32-5. PMID: 24579068.
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    18. Natsuizaka M, Kinugasa H, Kagawa S, Whelan KA, Naganuma S, Subramanian H, Chang S, Nakagawa KJ, Rustgi NL, Kita Y, Natsugoe S, Basu D, Gimotty PA, Klein-Szanto AJ, Diehl JA, Nakagawa H. IGFBP3 promotes esophageal cancer growth by suppressing oxidative stress in hypoxic tumor microenvironment. Am J Cancer Res. 2014; 4(1):29-41. PMID: 24482736.
      View in: PubMed
    19. Joshi RP, Schmidt AM, Das J, Pytel D, Riese MJ, Lester M, Diehl JA, Behrens EM, Kambayashi T, Koretzky GA. The ? isoform of diacylglycerol kinase plays a predominant role in regulatory T cell development and TCR-mediated ras signaling. Sci Signal. 2013 Nov 26; 6(303):ra102. PMID: 24280043.
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    20. Lee EK, Lian Z, D'Andrea K, Letrero R, Sheng W, Liu S, Diehl JN, Pytel D, Barbash O, Schuchter L, Amaravaradi R, Xu X, Herlyn M, Nathanson KL, Diehl JA. The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma. Mol Cell Biol. 2013 Nov; 33(22):4422-33. PMID: 24019069.
      View in: PubMed
    21. Basu D, Bewley AF, Sperry SM, Montone KT, Gimotty PA, Rasanen K, Facompre ND, Weinstein GS, Nakagawa H, Diehl JA, Rustgi AK, Herlyn M. EGFR inhibition promotes an aggressive invasion pattern mediated by mesenchymal-like tumor cells within squamous cell carcinomas. Mol Cancer Ther. 2013 Oct; 12(10):2176-86. PMID: 23939378.
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    22. Chitnis N, Pytel D, Diehl JA. UPR-inducible miRNAs contribute to stressful situations. Trends Biochem Sci. 2013 Sep; 38(9):447-52. PMID: 23906563.
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    23. Grugan KD, Vega ME, Wong GS, Diehl JA, Bass AJ, Wong KK, Nakagawa H, Rustgi AK. A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion. Cancer Biol Ther. 2013 Sep; 14(9):853-9. PMID: 23792586.
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    24. Young RM, Ackerman D, Quinn ZL, Mancuso A, Gruber M, Liu L, Giannoukos DN, Bobrovnikova-Marjon E, Diehl JA, Keith B, Simon MC. Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress. Genes Dev. 2013 May 15; 27(10):1115-31. PMID: 23699409.
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    25. Lee EK, Diehl JA. SCFs in the new millennium. Oncogene. 2014 Apr 17; 33(16):2011-8. PMID: 23624913.
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    26. Vaites LP, Lian Z, Lee EK, Yin B, DeMicco A, Bassing CH, Diehl JA. ATM deficiency augments constitutively nuclear cyclin D1-driven genomic instability and lymphomagenesis. Oncogene. 2014 Jan 02; 33(1):129-33. PMID: 23318439.
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    27. Sayers CM, Papandreou I, Guttmann DM, Maas NL, Diehl JA, Witze ES, Koong AC, Koumenis C. Identification and characterization of a potent activator of p53-independent cellular senescence via a small-molecule screen for modifiers of the integrated stress response. Mol Pharmacol. 2013 Mar; 83(3):594-604. PMID: 23229510.
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    28. Hart LS, Cunningham JT, Datta T, Dey S, Tameire F, Lehman SL, Qiu B, Zhang H, Cerniglia G, Bi M, Li Y, Gao Y, Liu H, Li C, Maity A, Thomas-Tikhonenko A, Perl AE, Koong A, Fuchs SY, Diehl JA, Mills IG, Ruggero D, Koumenis C. ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J Clin Invest. 2012 Dec; 122(12):4621-34. PMID: 23143306.
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    29. Yamane K, Hirose H, Bogar LJ, Cavarocchi NC, Diehl JT. Surgical treatment of infective endocarditis in patients undergoing chronic hemodialysis. J Heart Valve Dis. 2012 Nov; 21(6):774-82. PMID: 23409361.
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    30. Gao Y, Sartori DJ, Li C, Yu QC, Kushner JA, Simon MC, Diehl JA. PERK is required in the adult pancreas and is essential for maintenance of glucose homeostasis. Mol Cell Biol. 2012 Dec; 32(24):5129-39. PMID: 23071091.
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    31. Bhattacharya S, HuangFu WC, Dong G, Qian J, Baker DP, Karar J, Koumenis C, Diehl JA, Fuchs SY. Anti-tumorigenic effects of Type 1 interferon are subdued by integrated stress responses. Oncogene. 2013 Sep 05; 32(36):4214-21. PMID: 23045272.
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    32. Chitnis NS, Pytel D, Bobrovnikova-Marjon E, Pant D, Zheng H, Maas NL, Frederick B, Kushner JA, Chodosh LA, Koumenis C, Fuchs SY, Diehl JA. miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell. 2012 Nov 09; 48(3):353-64. PMID: 23022383.
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    33. Naganuma S, Whelan KA, Natsuizaka M, Kagawa S, Kinugasa H, Chang S, Subramanian H, Rhoades B, Ohashi S, Itoh H, Herlyn M, Diehl JA, Gimotty PA, Klein-Szanto AJ, Nakagawa H. Notch receptor inhibition reveals the importance of cyclin D1 and Wnt signaling in invasive esophageal squamous cell carcinoma. Am J Cancer Res. 2012; 2(4):459-75. PMID: 22860235.
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    34. Bobrovnikova-Marjon E, Pytel D, Riese MJ, Vaites LP, Singh N, Koretzky GA, Witze ES, Diehl JA. PERK utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate Akt activation, and promote adipocyte differentiation. Mol Cell Biol. 2012 Jun; 32(12):2268-78. PMID: 22493067.
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    35. Yamane K, Hirose H, Youdelman BA, Diehl JT. Thickened ascending aortic wall mimicking intramural hematoma. Asian Cardiovasc Thorac Ann. 2012 Apr; 20(2):208-9. PMID: 22499977.
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    36. Valvezan AJ, Zhang F, Diehl JA, Klein PS. Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity. J Biol Chem. 2012 Feb 03; 287(6):3823-32. PMID: 22184111.
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    37. Schoppy DW, Ragland RL, Gilad O, Shastri N, Peters AA, Murga M, Fernandez-Capetillo O, Diehl JA, Brown EJ. Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR. J Clin Invest. 2012 Jan; 122(1):241-52. PMID: 22133876.
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    38. Vaites LP, Lee EK, Lian Z, Barbash O, Roy D, Wasik M, Klein-Szanto AJ, Rustgi AK, Diehl JA. The Fbx4 tumor suppressor regulates cyclin D1 accumulation and prevents neoplastic transformation. Mol Cell Biol. 2011 Nov; 31(22):4513-23. PMID: 21911473.
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    39. Ohashi S, Natsuizaka M, Naganuma S, Kagawa S, Kimura S, Itoh H, Kalman RA, Nakagawa M, Darling DS, Basu D, Gimotty PA, Klein-Szanto AJ, Diehl JA, Herlyn M, Nakagawa H. A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factors. Cancer Res. 2011 Nov 01; 71(21):6836-47. PMID: 21890822.
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    40. Yamane K, Hirose H, Youdelman BA, Bogar LJ, Diehl JT. Conventional aortic valve replacement for elderly patients in the current era. Circ J. 2011; 75(11):2692-8. PMID: 21857141.
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    41. Hirose H, Yamane K, Youdelman BA, Bogar L, Diehl JT. Rigid sternal fixation improves postoperative recovery. Open Cardiovasc Med J. 2011; 5:148-52. PMID: 21760857.
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    42. Avivar-Valderas A, Salas E, Bobrovnikova-Marjon E, Diehl JA, Nagi C, Debnath J, Aguirre-Ghiso JA. PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol Cell Biol. 2011 Sep; 31(17):3616-29. PMID: 21709020.
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    43. Basu D, Montone KT, Wang LP, Gimotty PA, Hammond R, Diehl JA, Rustgi AK, Lee JT, Rasanen K, Weinstein GS, Herlyn M. Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas. Cell Cycle. 2011 Jun 15; 10(12):2008-16. PMID: 21558812.
      View in: PubMed
    44. Diehl JA, Fuchs SY, Koumenis C. The cell biology of the unfolded protein response. Gastroenterology. 2011 Jul; 141(1):38-41, 41.e1-2. PMID: 21620842.
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    45. Bhattacharya S, Qian J, Tzimas C, Baker DP, Koumenis C, Diehl JA, Fuchs SY. Role of p38 protein kinase in the ligand-independent ubiquitination and down-regulation of the IFNAR1 chain of type I interferon receptor. J Biol Chem. 2011 Jun 24; 286(25):22069-76. PMID: 21540188.
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    46. Stairs DB, Bayne LJ, Rhoades B, Vega ME, Waldron TJ, Kalabis J, Klein-Szanto A, Lee JS, Katz JP, Diehl JA, Reynolds AB, Vonderheide RH, Rustgi AK. Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell. 2011 Apr 12; 19(4):470-83. PMID: 21481789.
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    47. Barbash O, Lee EK, Diehl JA. Phosphorylation-dependent regulation of SCF(Fbx4) dimerization and activity involves a novel component, 14-3-3?. Oncogene. 2011 Apr 28; 30(17):1995-2002. PMID: 21242966.
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    48. Lee EK, Diehl JA. Breast cancer go sMAD: cyclin towards aggressive phenotypes. Cell Cycle. 2011 Jan 15; 10(2):187. PMID: 21239879.
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    49. Wang J, Reuschel EL, Shackelford JM, Jeang L, Shivers DK, Diehl JA, Yu XF, Finkel TH. HIV-1 Vif promotes the G1- to S-phase cell-cycle transition. Blood. 2011 Jan 27; 117(4):1260-9. PMID: 21149631.
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    50. Aggarwal P, Vaites LP, Kim JK, Mellert H, Gurung B, Nakagawa H, Herlyn M, Hua X, Rustgi AK, McMahon SB, Diehl JA. Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell. 2010 Oct 19; 18(4):329-40. PMID: 20951943.
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    51. Jiao P, Ma J, Feng B, Zhang H, Diehl JA, Chin YE, Yan W, Xu H. FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKKß pathways. Obesity (Silver Spring). 2011 Mar; 19(3):483-91. PMID: 20829802.
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    52. Ohashi S, Natsuizaka M, Yashiro-Ohtani Y, Kalman RA, Nakagawa M, Wu L, Klein-Szanto AJ, Herlyn M, Diehl JA, Katz JP, Pear WS, Seykora JT, Nakagawa H. NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology. 2010 Dec; 139(6):2113-23. PMID: 20801121.
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    53. Diehl JA, Ponugoti B. Ubiquitin-dependent proteolysis in G1/S phase control and its relationship with tumor susceptibility. Genes Cancer. 2010 Jul 01; 1(7):717-724. PMID: 21113395.
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    54. Diehl JA, Fuchs SY, Haines DS. Ubiquitin and cancer: new discussions for a new journal. Genes Cancer. 2010 Jul; 1(7):679-80. PMID: 21779465.
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    55. Grugan KD, Miller CG, Yao Y, Michaylira CZ, Ohashi S, Klein-Szanto AJ, Diehl JA, Herlyn M, Han M, Nakagawa H, Rustgi AK. Fibroblast-secreted hepatocyte growth factor plays a functional role in esophageal squamous cell carcinoma invasion. Proc Natl Acad Sci U S A. 2010 Jun 15; 107(24):11026-31. PMID: 20534479.
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    56. Michaylira CZ, Wong GS, Miller CG, Gutierrez CM, Nakagawa H, Hammond R, Klein-Szanto AJ, Lee JS, Kim SB, Herlyn M, Diehl JA, Gimotty P, Rustgi AK. Periostin, a cell adhesion molecule, facilitates invasion in the tumor microenvironment and annotates a novel tumor-invasive signature in esophageal cancer. Cancer Res. 2010 Jul 01; 70(13):5281-92. PMID: 20516120.
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    57. Natsuizaka M, Ohashi S, Wong GS, Ahmadi A, Kalman RA, Budo D, Klein-Szanto AJ, Herlyn M, Diehl JA, Nakagawa H. Insulin-like growth factor-binding protein-3 promotes transforming growth factor-{beta}1-mediated epithelial-to-mesenchymal transition and motility in transformed human esophageal cells. Carcinogenesis. 2010 Aug; 31(8):1344-53. PMID: 20513670.
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    58. Basu D, Nguyen TT, Montone KT, Zhang G, Wang LP, Diehl JA, Rustgi AK, Lee JT, Weinstein GS, Herlyn M. Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity. Oncogene. 2010 Jul 22; 29(29):4170-82. PMID: 20498638.
      View in: PubMed
    59. Ye J, Kumanova M, Hart LS, Sloane K, Zhang H, De Panis DN, Bobrovnikova-Marjon E, Diehl JA, Ron D, Koumenis C. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J. 2010 Jun 16; 29(12):2082-96. PMID: 20473272.
      View in: PubMed
    60. Bobrovnikova-Marjon E, Grigoriadou C, Pytel D, Zhang F, Ye J, Koumenis C, Cavener D, Diehl JA. PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage. Oncogene. 2010 Jul 08; 29(27):3881-95. PMID: 20453876.
      View in: PubMed
    61. Ohashi S, Natsuizaka M, Wong GS, Michaylira CZ, Grugan KD, Stairs DB, Kalabis J, Vega ME, Kalman RA, Nakagawa M, Klein-Szanto AJ, Herlyn M, Diehl JA, Rustgi AK, Nakagawa H. Epidermal growth factor receptor and mutant p53 expand an esophageal cellular subpopulation capable of epithelial-to-mesenchymal transition through ZEB transcription factors. Cancer Res. 2010 May 15; 70(10):4174-84. PMID: 20424117.
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    62. Zeng Z, Wang W, Yang Y, Chen Y, Yang X, Diehl JA, Liu X, Lei M. Structural basis of selective ubiquitination of TRF1 by SCFFbx4. Dev Cell. 2010 Feb 16; 18(2):214-25. PMID: 20159592.
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    63. Barbash O, Egan E, Pontano LL, Kosak J, Diehl JA. Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation. Oncogene. 2009 Dec 10; 28(49):4317-25. PMID: 19767775.
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    64. Bhattacharya S, HuangFu WC, Liu J, Veeranki S, Baker DP, Koumenis C, Diehl JA, Fuchs SY. Inducible priming phosphorylation promotes ligand-independent degradation of the IFNAR1 chain of type I interferon receptor. J Biol Chem. 2010 Jan 22; 285(4):2318-25. PMID: 19948722.
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    65. Kim JK, Diehl JA. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol. 2009 Aug; 220(2):292-6. PMID: 19415697.
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    66. He LM, Sartori DJ, Teta M, Opare-Addo LM, Rankin MM, Long SY, Diehl JA, Kushner JA. Cyclin D2 protein stability is regulated in pancreatic beta-cells. Mol Endocrinol. 2009 Nov; 23(11):1865-75. PMID: 19628581.
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    67. Pontano LL, Diehl JA. DNA damage-dependent cyclin D1 proteolysis: GSK3beta holds the smoking gun. Cell Cycle. 2009 Mar 15; 8(6):824-7. PMID: 19221502.
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    68. Liu J, HuangFu WC, Kumar KG, Qian J, Casey JP, Hamanaka RB, Grigoriadou C, Aldabe R, Diehl JA, Fuchs SY. Virus-induced unfolded protein response attenuates antiviral defenses via phosphorylation-dependent degradation of the type I interferon receptor. Cell Host Microbe. 2009 Jan 22; 5(1):72-83. PMID: 19154989.
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    69. Hamanaka RB, Bobrovnikova-Marjon E, Ji X, Liebhaber SA, Diehl JA. PERK-dependent regulation of IAP translation during ER stress. Oncogene. 2009 Feb 12; 28(6):910-20. PMID: 19029953.
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    70. Harada H, Nakagawa H, Takaoka M, Lee J, Herlyn M, Diehl JA, Rustgi AK. Cleavage of MCM2 licensing protein fosters senescence in human keratinocytes. Cell Cycle. 2008 Nov 15; 7(22):3534-8. PMID: 19001876.
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    71. Kalabis J, Oyama K, Okawa T, Nakagawa H, Michaylira CZ, Stairs DB, Figueiredo JL, Mahmood U, Diehl JA, Herlyn M, Rustgi AK. A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. J Clin Invest. 2008 Dec; 118(12):3860-9. PMID: 19033657.
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    72. Bobrovnikova-Marjon E, Hatzivassiliou G, Grigoriadou C, Romero M, Cavener DR, Thompson CB, Diehl JA. PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation. Proc Natl Acad Sci U S A. 2008 Oct 21; 105(42):16314-9. PMID: 18852460.
      View in: PubMed
    73. Barbash O, Diehl JA. SCF(Fbx4/alphaB-crystallin) E3 ligase: when one is not enough. Cell Cycle. 2008 Oct; 7(19):2983-6. PMID: 18818515.
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    74. Pontano LL, Aggarwal P, Barbash O, Brown EJ, Bassing CH, Diehl JA. Genotoxic stress-induced cyclin D1 phosphorylation and proteolysis are required for genomic stability. Mol Cell Biol. 2008 Dec; 28(23):7245-58. PMID: 18809569.
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    75. Liu L, Wise DR, Diehl JA, Simon MC. Hypoxic reactive oxygen species regulate the integrated stress response and cell survival. J Biol Chem. 2008 Nov 07; 283(45):31153-62. PMID: 18768473.
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    76. Pontano LL, Diehl JA. Speeding through cell cycle roadblocks: Nuclear cyclin D1-dependent kinase and neoplastic transformation. Cell Div. 2008 Sep 02; 3:12. PMID: 18764945.
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    77. Lioni M, Noma K, Snyder A, Klein-Szanto A, Diehl JA, Rustgi AK, Herlyn M, Smalley KS. Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway. Mol Cancer Ther. 2008 Sep; 7(9):2866-75. PMID: 18790767.
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    78. Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, Lu F, Rustgi AK, Diehl JA. Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Cancer Cell. 2008 Jul 08; 14(1):68-78. PMID: 18598945.
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    79. Lin DI, Aggarwal P, Diehl JA. Phosphorylation of MCM3 on Ser-112 regulates its incorporation into the MCM2-7 complex. Proc Natl Acad Sci U S A. 2008 Jun 10; 105(23):8079-84. PMID: 18524952.
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    80. Aggarwal P, Lessie MD, Lin DI, Pontano L, Gladden AB, Nuskey B, Goradia A, Wasik MA, Klein-Szanto AJ, Rustgi AK, Bassing CH, Diehl JA. Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication. Genes Dev. 2007 Nov 15; 21(22):2908-22. PMID: 18006686.
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    81. Plastaras JP, Kim SH, Liu YY, Dicker DT, Dorsey JF, McDonough J, Cerniglia G, Rajendran RR, Gupta A, Rustgi AK, Diehl JA, Smith CD, Flaherty KT, El-Deiry WS. Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res. 2007 Oct 01; 67(19):9443-54. PMID: 17909054.
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    82. Bobrovnikova-Marjon E, Diehl JA. Coping with stress: ATF6alpha takes the stage. Dev Cell. 2007 Sep; 13(3):322-4. PMID: 17765676.
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    83. Lin DI, Lessie MD, Gladden AB, Bassing CH, Wagner KU, Diehl JA. Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene. 2008 Feb 21; 27(9):1231-42. PMID: 17724472.
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    84. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell. 2007 Apr; 11(4):335-47. PMID: 17418410.
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    85. Barbash O, Lin DI, Diehl JA. SCF Fbx4/alphaB-crystallin cyclin D1 ubiquitin ligase: a license to destroy. Cell Div. 2007 Jan 15; 2:2. PMID: 17224055.
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    86. Lin DI, Barbash O, Kumar KG, Weber JD, Harper JW, Klein-Szanto AJ, Rustgi A, Fuchs SY, Diehl JA. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell. 2006 Nov 03; 24(3):355-66. PMID: 17081987.
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    87. Oyama K, Okawa T, Nakagawa H, Takaoka M, Andl CD, Kim SH, Klein-Szanto A, Diehl JA, Herlyn M, El-Deiry W, Rustgi AK. AKT induces senescence in primary esophageal epithelial cells but is permissive for differentiation as revealed in organotypic culture. Oncogene. 2007 Apr 05; 26(16):2353-64. PMID: 17043653.
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    88. Zhang F, Hamanaka RB, Bobrovnikova-Marjon E, Gordan JD, Dai MS, Lu H, Simon MC, Diehl JA. Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest. J Biol Chem. 2006 Oct 06; 281(40):30036-45. PMID: 16893887.
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    89. Schnepp RW, Chen YX, Wang H, Cash T, Silva A, Diehl JA, Brown E, Hua X. Mutation of tumor suppressor gene Men1 acutely enhances proliferation of pancreatic islet cells. Cancer Res. 2006 Jun 01; 66(11):5707-15. PMID: 16740708.
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    90. Benzeno S, Lu F, Guo M, Barbash O, Zhang F, Herman JG, Klein PS, Rustgi A, Diehl JA. Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1. Oncogene. 2006 Oct 12; 25(47):6291-303. PMID: 16732330.
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    91. Marzec M, Kasprzycka M, Lai R, Gladden AB, Wlodarski P, Tomczak E, Nowell P, Deprimo SE, Sadis S, Eck S, Schuster SJ, Diehl JA, Wasik MA. Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity. Blood. 2006 Sep 01; 108(5):1744-50. PMID: 16690963.
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    92. Knudsen KE, Diehl JA, Haiman CA, Knudsen ES. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 2006 Mar 13; 25(11):1620-8. PMID: 16550162.
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    93. Kandel R, Li SQ, Bell R, Wunder J, Ferguson P, Kauzman A, Diehl JA, Werier J. Cyclin D1 and p21 is elevated in the giant cells of giant cell tumors. J Orthop Res. 2006 Mar; 24(3):428-37. PMID: 16479604.
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    94. Gladden AB, Woolery R, Aggarwal P, Wasik MA, Diehl JA. Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma. Oncogene. 2006 Feb 16; 25(7):998-1007. PMID: 16247460.
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    95. Gladden AB, Diehl JA. Location, location, location: the role of cyclin D1 nuclear localization in cancer. J Cell Biochem. 2005 Dec 01; 96(5):906-13. PMID: 16163738.
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    96. Cullinan SB, Diehl JA. Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol. 2006 Mar; 38(3):317-32. PMID: 16290097.
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    97. Hamanaka RB, Bennett BS, Cullinan SB, Diehl JA. PERK and GCN2 contribute to eIF2alpha phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway. Mol Biol Cell. 2005 Dec; 16(12):5493-501. PMID: 16176978.
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    98. Diehl JA, Benzeno S. Cyclin D1 and pancreatic carcinoma: a proliferative agonist and chemotherapeutic antagonist. Clin Cancer Res. 2005 Aug 15; 11(16):5665-7. PMID: 16115900.
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    99. Ma Y, Feng Q, Sekula D, Diehl JA, Freemantle SJ, Dmitrovsky E. Retinoid targeting of different D-type cyclins through distinct chemopreventive mechanisms. Cancer Res. 2005 Jul 15; 65(14):6476-83. PMID: 16024653.
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    100. Pastuszko P, Eisenberg JA, Diehl JT. Ductus arteriosus aneurysm in an adult patient presenting with hoarseness. J Card Surg. 2005 Jul-Aug; 20(4):386-8. PMID: 15985147.
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    101. Benzeno S, Diehl JA. A novel WISp39 protein links Hsp90 and p21 stability to the G2/M checkpoint. Cancer Biol Ther. 2005 Apr; 4(4):376-8. PMID: 15846062.
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    102. Petre-Draviam CE, Williams EB, Burd CJ, Gladden A, Moghadam H, Meller J, Diehl JA, Knudsen KE. A central domain of cyclin D1 mediates nuclear receptor corepressor activity. Oncogene. 2005 Jan 13; 24(3):431-44. PMID: 15558026.
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    103. Benzeno S, Diehl JA. C-terminal sequences direct cyclin D1-CRM1 binding. J Biol Chem. 2004 Dec 31; 279(53):56061-6. PMID: 15513923.
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    104. Cullinan SB, Gordan JD, Jin J, Harper JW, Diehl JA. The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol Cell Biol. 2004 Oct; 24(19):8477-86. PMID: 15367669.
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    105. Lin DI, Diehl JA. Mechanism of cell-cycle control: ligating the ligase. Trends Biochem Sci. 2004 Sep; 29(9):453-5. PMID: 15337116.
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    106. Benzeno S, Narla G, Allina J, Cheng GZ, Reeves HL, Banck MS, Odin JA, Diehl JA, Germain D, Friedman SL. Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. Cancer Res. 2004 Jun 01; 64(11):3885-91. PMID: 15172998.
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    107. Rodriguez E, Park P, Cowan S, Weinstein M, Kaulback K, Friedberg JS, Diehl JT, Mannion JD, Cohen M. Complicated management of a traumatic aortoesophageal fistula in a patient with a right-sided aortic arch. J Trauma. 2004 Mar; 56(3):691-3. PMID: 15128145.
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    108. Cullinan SB, Diehl JA. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem. 2004 May 07; 279(19):20108-17. PMID: 14978030.
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    109. Diehl JA. The cyclin D3 knockout: a pound of redundancy with a dash of tissue specificity. Cancer Biol Ther. 2004 Feb; 3(2):162-4. PMID: 14752277.
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    110. Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res. 2003 Nov 01; 63(21):7056-61. PMID: 14612495.
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    111. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O'Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003 Nov 18; 108(20):2460-6. PMID: 14581396.
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