Expression of p16INK4A variants in senescent human fibroblasts independent of protein phosphorylation

Journal of Cellular Biochemistry

Volumn 94, Issue 6, 2005, Pages 1135-1147

  Weebadda, Wineeta K C ^a   Jackson, Tonya J ^a   Lin, Athena W ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

2D SDS PAGE; Cdk; Human fibroblasts; Oncogenic ras; p16; Proteomics; Quiescence; Senescence

Indexed keywords

ANTIBODY; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; PHOSPHATASE; PHOSPHOPROTEIN; PHOSPHOSERINE; PROTEIN P16; PROTEIN P16INK4A; TUMOR SUPPRESSOR PROTEIN; CDK4 PROTEIN, HUMAN; CDK6 PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE; ONCOPROTEIN;

ACIDITY; ARTICLE; CELL AGING; CELL CULTURE; CONTROLLED STUDY; FIBROBLAST; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; ISOELECTRIC FOCUSING; ONCOGENE H RAS; OSTEOSARCOMA CELL; PHENOTYPE; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN VARIANT; STARVATION; TWO DIMENSIONAL ELECTROPHORESIS; CULTURE MEDIUM; METABOLISM; PHOSPHORYLATION; WESTERN BLOTTING;

BLOTTING, WESTERN; CELL AGING; CULTURE MEDIA, SERUM-FREE; CYCLIN-DEPENDENT KINASE 4; CYCLIN-DEPENDENT KINASE 6; CYCLIN-DEPENDENT KINASE INHIBITOR P16; CYCLIN-DEPENDENT KINASES; ELECTROPHORESIS, POLYACRYLAMIDE GEL; FIBROBLASTS; HUMANS; IMMUNOPRECIPITATION; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS;

EID: 26444531683     PISSN: 07302312     EISSN: None     Source Type: Journal    
DOI: 10.1002/jcb.20372     Document Type: Article

References (74)

1. Aagaard L, Lukas J, Bartkova J, Kjerulff AA, Strauss M, Bartek J. 1995. Aberrations of p16Ink4 and retinoblastoma tumour-suppressor genes occur in distinct sub-sets of human cancer cell lines. Int J Cancer 61:115-120.
2. Alani RM, Young AZ, Shifflett CB. 2001. Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a. Proc Natl Acad Sci USA 98:7812-7816.
3. Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC. 1996. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci USA 93:13742-13747.
4. Aletta JM, Cimato TR, Ettinger MJ. 1998. Protein methylation: A signal event in post-translational modification. Trends Biochem Sci 23:89-91.
5. Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J. 2003. Reversal of human cellular senescence: Roles of the p53 and p16 pathways. Embo J 22:4212-4222.
6. Berkelman T, Stestedt T. 2004. 2-D electrophoresis principals and methods. Uppasala, Switzerland: Amersham Biosciences.
7. Bjellqvist B, Hughes GJ, Pasquali C, Paquet N, Ravier F, Sanchez JC, Frutiger S, Hochstrasser D. 1993. The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences. Electrophoresis 14:1023-1031.
8. Bjellqvist B, Basse B, Olsen E, Celis JE. 1994. Reference points for comparisons of two-dimensional maps of proteins from different human cell types defined in a pH scale where isoelectric points correlate with polypeptide compositions. Electrophoresis 15:529-539.
9. Bond JA, Blaydes JP, Rowson J, Haughton MF, Smith JR, Wynford-Thomas D, Wyllie FS. 1995. Mutant p53 rescues human diploid cells from senescence without inhibiting the induction of SDI1/WAF1. Cancer Res 55:2404-2409.
10. Brookes S, Rowe J, Ruas M, Llanos S, Clark PA, Lomax M, James MC, Vatcheva R, Bates S, Vousden KH, Parry D, Gruis N, Smit N, Bergman W, Peters G. 2002. INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. Embo J 21:2936-2945.
11. Burmer GC, Rabinovitch PS, Norwood TH. 1984. Evidence for differences in the mechanism of cell cycle arrest between senescent and serum-deprived human fibroblasts: Heterokaryon and metabolic inhibitor studies. J Cell Physiol 118:97-103.
12. Campisi J. 2001. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol 11:S27-S31.
13. Campisi J. 2003. Analysis of tumor suppressor gene-induced senescence. Methods Mol Biol 223:155-172.
14. Chen Q, Fischer A, Reagan JD, Yan LJ, Ames BN. 1995. Oxidative DNA damage and senescence of human diploid flbroblast cells. Proc Natl Acad Sci USA 92:4337-4341.
15. Cimato TR, Tang J, Xu Y, Guarnaccia C, Herschman HR, Pongor S, Aletta JM. 2002. Nerve growth factor-mediated increases in protein methylation occur predominantly at type I arginine methylation sites and involve protein arginine methyltransferase 1. J Neurosci Res 67:435-442.
16. Cunningham JJ, Roussel MF. 2001. Cyclin-dependent kinase inhibitors in the development of the central nervous system. Cell Growth Differ 12:387-396.
17. Deng Q, Liao R, Wu BL, Sun P. 2004. High intensity ras signaling induces premature senescence by activating p38 pathway in primary human fibroblasts. J Biol Chem 279:1050-1059.
18. Dimri GP, Campisi J. 1994. Molecular and cell biology of replicative senescence. Cold Spring Harb Symp Quant Biol 59:67-73.
19. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al. 1995. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363-9367.
20. Drayton S, Rowe J, Jones R, Vatcheva R, Cuthbert-Heavens D, Marshall J, Fried M, Peters G. 2003. Tumor suppressor p16INK4a determines sensitivity of human cells to transformation by cooperating cellular oncogenes. Cancer Cell 4:301-310.
21. Erickson S, Sangfelt O, Heyman M, Castro J, Einhorn S, Grander D. 1998. Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence. Oncogene 17:595-602.
22. Ferbeyre G, de Stanchina E, Lin AW, Querido E, McCurrach ME, Hannon GJ, Lowe SW. 2002. Oncogenic ras and p53 cooperate to induce cellular senescence. Mol Cell Biol 22:3497-3508.
23. Florl AR, Franke KH, Niederacher D, Gerharz CD, Seifert HH, Schulz WA. 2000. DNA methylation and the mechanisms of CDKN2A inactivation in transitional cell carcinoma of the urinary bladder. Lab Invest 80:1513-1522.
24. Gump J, Stokoe D, McCormick F. 2003. Phosphorylation of p16INK4A correlates with Cdk4 association. J Biol Chem 278:6619-6622.
25. Kara E, Tsurui H, Shinozaki A, Nakada S, Oda K. 1991. Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. Biochem Biophys Res Commun 179:528-534.
26. Hara E, Smith R, Parry D, Tahara H, Stone S, Peters G. 1996. Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cell Biol 16:859-867.
27. Harland M, Meloni R, Gruis N, Pinney E, Brookes S, Spurr NK, Frischauf AM, Bataille V, Peters G, Cuzick J, Selby P, Bishop DT, Bishop JN. 1997. Germline mutations of the CDKN2 gene in UK melanoma families. Hum Mol Genet 6:2061-2067.
28. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM. 2004. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14:501-513.
29. Huot TJ, Rowe J, Harland M, Drayton S, Brookes S, Gooptu C, Purkis P, Fried M, Bataille V, Hara E, Newton-Bishop J, Peters G. 2002. Biallelic mutations in p16(INK4a) confer resistance to Ras- and Ets-induced senescence in human diploid fibroblasts. Mol Cell Biol 22:8135-8143.
30. Itahana K, Zou Y, Itahana Y, Martinez JL, Beausejour C, Jacobs JJ, Van Lohuizen M, Band V, Campisi J, Dimri GP. 2003. Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1. Mol Cell Biol 23:389-401.
31. Jacobs JJ, Kieboom K, Marino S, DePinho RA, van Lohuizen M. 1999. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397:164-168.
32. Jarrard DF, Sarkar S, Shi Y, Yeager TR, Magrane G, Kinoshita H, Nassif N, Meisner L, Newton MA, Waldman FM, Reznikoff CA. 1999. p16/pRb pathway alterations are required for bypassing senescence in human prostate epithelial cells. Cancer Res 59:2957-2964.
33. Khleif SN, DeGregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, Howley PM. 1996. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci USA 93:4350-4354.
34. Laemmli UK. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685.
35. Lin AW, Lowe SW. 2001. Oncogenic ras activates the ARF-p53 pathway to suppress epithelial cell transformation. Proc Natl Acad Sci USA 98:5025-5030.
36. Lin AW, Barradas M, Stone JC, van Aelst L, Serrano M, Lowe SW. 1998. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev 12:3008-3019.
37. Loo JC, Liu L, Hao A, Gao L, Agatep R, Shennan M, Summers A, Goldstein AM, Tucker MA, Deters C, Fusaro R, Blazer K, Weitzel J, Lassam N, Lynch H, Hogg D. 2003. Germline splicing mutations of CDKN2A predispose to melanoma. Oncogene 22:6387-6394.
38. Lukas J, Aagaard L, Strauss M, Bartek J. 1995a. Oncogenic aberrations of p16INK4/CDKN2 and cyclin D1 cooperate to deregulate G1 control. Cancer Res 55:4818-4823.
39. Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, Peters G, Bartek J. 1995b. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375:503-506.
40. Macip S, Igarashi M, Fang L, Chen A, Pan ZQ, Lee SW, Aaronson SA. 2002. Inhibition of p21-mediated ROS accumulation can rescue p21-induced senescence. Embo J 21:2180-2188.
41. Mallette FA, Goumard S, Gaumont-Leclerc MF, Moiseeva O, Ferbeyre G. 2004. Human fibroblasts require the Rb family of tumor suppressors, but not p53, for PML-induced senescence. Oncogene 23:91-99.
42. Mathon NF, Lloyd AC. 2001. Cell senescence and cancer. Nat Rev Cancer 1:203-213.
43. McConnell BB, Starborg M, Brookes S, Peters G. 1998. Inhibitors of cyclin-dependent kinases induce features of replicative senescence in early passage human diploid fibroblasts. Curr Biol 8:351-354.
44. Medema RH, Herrera RE, Lam F, Weinberg RA. 1995. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci USA 92:6289-6293.
45. Murray AW. 2004. Recycling the cell cycle: Cyclins revisited. Cell 116:221-234.
46. Narita M, Nunez S, Heard E, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW. 2003. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703-716.
47. Nishiwaki E, Turner SL, Harju S, Miyazaki S, Kashiwagi M, Koh J, Serizawa H. 2000. Regulation of CDK7-carboxyl-terminal domain kinase activity by the tumor suppressor p16(INK4A) contributes to cell cycle regulation. Mol Cell Biol 20:7726-7734.
48. Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G, Hara E. 2001. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. Nature 409:1067-1070.
49. Okamoto A, Demetrick DJ, Spillare EA, Hagiwara K, Hussain SP, Bennett WP, Forrester K, Gerwin B, Serrano M, Beach DH, et al. 1994. Mutations and altered expression of p16INK4 in human cancer. Proc Natl Acad Sci USA 91:11045-11049.
50. Palmero I, Pantoja C, Serrano M. 1998. p19ARF links the tumour suppressor p53 to Ras. Nature 395:125-126.
51. Parry D, Peters G. 1996. Temperature-sensitive mutants of p16CDKN2 associated with familial melanoma. Mol Cell Biol 16:3844-3852.
52. Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massague J. 1994. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 78:59-66.
53. Puthenveettil JA, Burger MS, Reznikoff CA. 1999. Replicative senescence in human uroepithelial cells. Adv Exp Med Biol 462:83-91.
54. Rabilloud T. 2000. Detecting proteins separated by 2-D gel electrophoresis. Anal Chem 72:48A-55A.
55. Ranade K, Hussussian CJ, Sikorski RS, Varmus HE, Goldstein AM, Tucker MA, Serrano M, Hannon GJ, Beach D, Dracopoli NC. 1995. Mutations associated with familial melanoma impair p16INK4 function. Nat Genet 10:114-116.
56. Rocco JW, Sidransky D. 2001. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res 264:42-55.
57. Ruas M, Peters G. 1998. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1378: F115-F77.
58. Ruas M, Brookes S, McDonald NQ, Peters G. 1999. Functional evaluation of tumour-specific variants of p16INK4a/CDKN2A: Correlation with protein structure information. Oncogene 18:5423-5434.
59. Sandhu C, Peehl DM, Slingerland J. 2000. p16INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells. Cancer Res 60:2616-2622.
60. Serizawa H. 1998. Cyclin-dependent kinase inhibitor p16INK4A inhibits phosphorylation of RNA polymerase II by general transcription factor TFIIH. J Biol Chem 273:5427-5430.
61. Serrano M. 1997. The tumor suppressor protein p16INK4a. Exp Cell Res 237:7-13.
62. Serrano M, Hannon GJ, Beach D. 1993. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704-707.
63. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593-602.
64. Sharpless NE, Bardeesy N, Lee KH, Carrasco D, Castrillon DH, Aguirre AJ, Wu EA, Horner JW, DePinho RA. 2001. Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis. Nature 413:86-91.
65. Shay JW, Roninson IB. 2004. Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene 23:2919-2933.
66. Sherr CJ. 2000. Cell cycle control and cancer. Harvey Lect 96:73-92.
67. Sherr CJ, Roberts JM. 1995. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9:1149-1163.
68. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. 2002. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 62:1876-1883.
69. Wei W, Herbig U, Wei S, Dutriaux A, Sedivy JM. 2003. Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts. EMBO Rep 4:1061-1066.
70. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. 1993. p21 is a universal inhibitor of cyclin kinases. Nature 366:701-704.
71. Xiong Y, Kuppuswamy D, Li Y, Livanos EM, Hixon M, White A, Beach D, Tlsty TD. 1996. Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation. J Virol 70:999-1008.
72. Yeager T, Stadler W, Belair C, Puthenveettil J, Olopade O, Reznikoff C. 1995. Increased p16 levels correlate with pRb alterations in human urothelial cells. Cancer Res 55:493-497.
73. Zebedee Z, Hara E. 2001. Id proteins in cell cycle control and cellular senescence. Oncogene 20:8317-8325.
74. Zhu J, Woods D, McMahon M, Bishop JM. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev 12:2997-3007.