Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues

Cancer Research

Volumn 67, Issue 10, 2007, Pages 4732-4741

  Ramsey, Matthew R ^a   Krishnamurthy, Janakiraman ^a   Pei, Xin Hai ^a   Torrice, Chad ^a   Lin, Weili ^a   Carrasco, Daniel R ^b,c   Ligon, Keith L ^c   Xiong, Yue ^a   Sharpless, Norman E ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; CYCLIN DEPENDENT KINASE INHIBITOR; CYCLIN DEPENDENT KINASE INHIBITOR 2C; MESSENGER RNA; PD 0332991; PROTEIN P16INK4A; UNCLASSIFIED DRUG; 6 ACETYL 8 CYCLOPENTYL 5 METHYL 2 (5 PIPERAZIN 1 YLPYRIDIN 2 YLAMINO) 8H PYRIDO(2,3 D)PYRIMIDIN 7 ONE; 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-(5-PIPERAZIN-1-YLPYRIDIN-2-YLAMINO)-8H-PYRIDO(2,3-D)PYRIMIDIN-7-ONE; CDKN2C PROTEIN, MOUSE; CYCLIN DEPENDENT KINASE 5; PIPERAZINE DERIVATIVE; PYRIDINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG EFFECT; ENZYME ACTIVITY; FIBROBLAST; HYPOPHYSIS TUMOR; MOUSE; NONHUMAN; PANCREAS ISLET; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; ANIMAL; BIOSYNTHESIS; CELL GROWTH; CELL TRANSFORMATION; CYTOLOGY; DRUG ANTAGONISM; EMBRYO; ENZYMOLOGY; GENETICS; METABOLISM; PATHOLOGY; PHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; CELL GROWTH PROCESSES; CELL TRANSFORMATION, NEOPLASTIC; CYCLIN-DEPENDENT KINASE 5; CYCLIN-DEPENDENT KINASE 6; CYCLIN-DEPENDENT KINASE INHIBITOR P16; CYCLIN-DEPENDENT KINASE INHIBITOR P18; EMBRYO; FIBROBLASTS; MICE; MICE, TRANSGENIC; PIPERAZINES; PITUITARY NEOPLASMS; PYRIDINES;

EID: 34250372017     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-06-3437     Document Type: Article

References (48)

1. Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci 2005;30:630-41.
2. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993;366:704-7.
3. Hannon GJ, Beach D. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 1994;371: 257-61.
4. Guan KL, Jenkins CW, Li Y, et al. Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Genes Dev 1994;8:2939-52.
5. Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol Cell Biol 1995;15:2672-81.
6. Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1998; 1378:F115-77.
7. Brotherton DH, Dhanaraj V, Wick S, et al. Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d. Nature 1998;395:244-50.
8. Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP. Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. Nature 1998;395:237-43.
9. Thullberg M, Bartek J, Lukas J. Ubiquitin/proteasome-mediated degradation of p19INK4d determines its periodic expression during the cell cycle. Oncogene 2000;19:2870-6.
10. Phelps DE, Hsiao KM, Li Y, et al. Coupled transcriptional and translational control of cyclin-dependent kinase inhibitor p18INK4c expression during myogenesis. Mol Cell Biol 1998;18:2334-43.
11. Gump J, Stokoe D, McCormick F. Phosphorylation of p16INK4A correlates with Cdk4 association. J Biol Chem 2003;278:6619-22.
12. Thullberg M, Bartkova J, Khan S, et al. Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. FEBS Lett 2000;470:161-6.
13. Sharpless NE. INK4a/ARF: a multifunctional tumor suppressor locus. Mutat Res 2005;576:22-38.
14. Zindy F, van Deursen J, Grosveld G, Sherr CJ, Roussel MF. INK4d-deficient mice are fertile despite testicular atrophy. Mol Cell Biol 2000;20:372-8.
15. Chen P, Zindy F, Abdala C, et al. Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nat Cell Biol 2003;5:422-6.
16. Latres E, Malumbres M, Sotillo R, et al. Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis. EMBO J 2000;19:3496-506.
17. Krimpenfort P, Quon KC, Mooi WJ, Loonstra A, Berns A. Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice. Nature 2001;413:83-6.
18. Sharpless NE, Bardeesy N, Lee KH, et al. Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis. Nature 2001;413:86-91.
19. Sharpless NE, Ramsey MR, Balasubramanian P, Castrillon DH, DePinho RA. The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and tumorigenesis. Oncogene 2004;23:379-85.
20. Franklin DS, Godfrey VL, Lee H, et al. CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. Genes Dev 1998;12:2899-911.
21. Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 2004;3:1427-38.
22. Sharpless NE, Alson S, Chan S, Silver DP, Castrillon DH, DePinho RA. p16(INK4a) and p53 deficiency cooperate in tumorigenesis. Cancer Res 2002;62: 2761-5.
23. Miliani de Marval PL, Macias E, Rounbehler R, et al. Lack of cyclin-dependent kinase 4 inhibits c-myc tumorigenic activities in epithelial tissues. Mol Cell Biol 2004;24:7538-47.
24. Krishnamurthy J, Torrice C, Kamsey MR, et al. Ink4a/Arf expression is a biomarker of aging. J Clin Invest 2004;114:1299-307.
25. Krishnamurthy J, Ramsey MR, Ligon KL, et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 2006;443:453-7.
26. Palmero I, McConnell B, Parry D, et al. Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status. Oncogene 1997;15:495-503.
27. Zindy F, Quelle DE, Roussel MF, Sherr CJ. Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene 1997;15:203-11.
28. Zindy F, den Besten W, Chen B, et al. Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18(Ink4c) and pl9(Ink4d). Mol Cell Biol 2001;21:3244-55.
29. Sotillo R, Dubus P, Martin J, et al. Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J 2001;20:6637-47.
30. Rane SG, Cosenza SC, Mettus RV, Reddy EP. Germ line transmission of the Cdk4(R24C) mutation facilitates tumorigenesis and escape from cellular senescence. Mol Cell Biol 2002;22:644-56.
31. Hu N, Gutsmann A, Herbert DC, Bradley A, Lee WH, Lee EY. Heterozygous Rb-1 delta 20/+ mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance. Oncogene 1994;9:1021-7.
32. Tsutsui T, Hesabi B, Moons DS, et al. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27(Kip1) activity. Mol Cell Biol 1999;19: 7011-9.
33. Rane SG, Dubus P, Mettus RV, et al. Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia. Nat Genet 1999;22:44-52.
34. Pei XH, Bai F, Tsutsui T, Kiyokawa H, Xiong Y. Genetic evidence for functional dependency of p18Ink4c on Cdk4. Mol Cell Biol 2004;24:6653-64.
35. Georgia S, Bhushan A. Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest 2004;114:963-8.
36. Kozar K, Ciemerych MA, Rebel VI, et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell 2004;118:477-91.
37. Malumbres M, Sotillo R, Santamaria D, et al. Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Cell 2004;118: 493-504.
38. Toogood PL, Harvey PJ, Repine JT, et al. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6. J Med Chem 2005;48:2388-406.
39. Tourigny MR, Ursini-Siegel J, Lee H, et al. CDK inhibitor p18(INK4c) is required for the generation of functional plasma cells. Immunity 2002;17:179-89.
40. Tam SW, Shay JW, Pagano M. Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 inhibitor p16Ink4. Cancer Res 1994;54:5816-20.
41. Li Y, Nichols MA, Shay JW, Xiong Y. Transcriptional repression of the D-type cyclin-dependent kinase inhibitor pl6 by the retinoblastoma susceptibility gene product pRb. Cancer Res 1994;54:6078-82.
42. Khleif SN, DeGregori J, Yee CL, et al. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci USA 1996;93:4350-4.
43. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y. pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes Dev 2007;21:49-54.
44. Jacobs JJ, Kieboom K, Marino S, DePinho RA, van Lohuizen M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 1999; 397:164-8.
45. Itahana K, Zou Y, Itahana Y, et al. Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1. Mol Cell Biol 2003;23: 389-401.
46. Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P. Cdk2 knockout mice are viable. Curr Biol 2003;13: 1775-85.
47. Ortega S, Prieto I, Odajima J, et al. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 2003;35:25-31.
48. Geng Y, Yu Q, Sicinska E, et al. Cyclin E ablation in the mouse. Cell 2003;114:431-43.