Abstract
The retinoblastoma family of proteins including pRB, p107 and p130 undergoes cell cycle dependent phosphorylation during the mid-G1 to S phase transition. This phosphorylation is dependent upon the activity of cyclin D/cdk4. In contrast to pRB and p107, p130 is phosphorylated during G0 and the early G1 phase of the cell cycle. We observed that p130 is specifically phosphorylated on serine and threonine residues in T98G cells arrested in G0 by serum deprivation or density arrest. Identification of the phospho-serine and phospho-threonine residues revealed that most were clustered within a short co-linear region unique to p130, defined as the Loop. Deletion of the Loop region resulted in a change in the phosphorylation status of p130 under growth arrest conditions. Notably, deletion of the Loop did not affect the ability of p130 to bind to E2F-4 or SV40 Large T antigen, to induce growth arrest in Saos-2 cells, and to become hyperphosphorylated during the proliferative phase of the cell cycle. p130 undergoes specific G0 phosphorylation in a manner that distinguishes it from pRB and p107.
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References
Bookstein R, Shew JY, Chen PL, Scully P and Lee WH. . 1990 Science 247: 712–715.
Boyle WJ, van der Geer P and Hunter T. . 1991 Methods in Enzymology 201: 110–149.
Chittum HS, Lane WS, Carlson BA, Roller PP, Lung FD, Lee BJ and Hatfield DL. . 1998 Biochemistry 37: 10866–10870.
Christensen JB and Imperiale MJ. . 1995 J. Virol. 69: 3945–3948.
Cinti C, Claudio PP, Howard CM, Neri LM, Fu Y, Leoncini L, Tosi GM, Maraldi NM and Giordano A. . 2000 Cancer Res. 60: 383–389.
Claudio PP, De Luca A, Howard CM, Baldi A, Firpo EJ, Koff A, Paggi MG and Giordano A. . 1996 Cancer Res. 56: 2003–2008.
Claudio PP, Howard CM, Baldi A, DeLuca A, Fu Y, Condorelli G, Sun Y, Colburn N, Calabretta B and Giordano A. . 1994 Cancer Res. 54: 5556–5560.
Claudio PP, Howard CM, Fu Y, Cinti C, Califano L, Micheli P, Mercer EW, Caputi M and Giordano A. . 2000a) Cancer Res. 60: 8–12.
Claudio PP, Howard CM, Pacilio C, Cinti C, Ramano G, Minimo C, Maraldi NM, Minna JD, Gelbert L, Leoncini L, Tosi GM, Hicheli P, Caputi M, Giordano GG and Giordano A. . 2000b Cancer Res. 60: 372–382.
Cobrinik D, Whyte P, Peeper DS, Jacks T and Weinberg RA. . 1993 Genes Dev. 7: 2392–2404.
DeCaprio JA, Furukawa Y, Ajchenbaum F, Griffin JD and Livingston DM. . 1992 Proc. Natl. Acad. Sci. USA 89: 1795–1798.
DeCaprio JA, Ludlow JW, Figge J, Shew J-Y, Huang C-M, Lee W-H, Marsilio E, Paucha E and Livingston DM. . 1988 Cell 54: 275–283.
DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang C-M and Livingston DM. . 1989 Cell 58: 1085–1095.
Dyson N. . 1998 Genes Dev. 12: 2245–2262.
Dyson N, Buchkovich, K, Whyte P and Harlow E. . 1989a Cell 58: 249–255.
Dyson N, Howley PM, Munger K and Harlow E. . 1989b Science 243: 934–937.
Ewen ME, Ludlow JW, Marsilio E, DeCaprio JA, Millikan RC, Cheng SH, Paucha E and Livingston DM. . 1989 Cell 58: 257–267.
Ewen ME, Xing Y, Lawrence JB and Livingston DM. . 1991 Cell 66: 1155–1164.
Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM and Dryja TP. . 1986 Nature 323: 643–646.
Furukawa Y, Iwase S, Kikuchi J, Nakamura M, Yamada H and Matsuda M. . 1999 Oncogene 18: 2003–2014.
Garriga J, Limon A, Mayol X, Rane SG, Albrecht JH, Reddy EP, Andres V and Grana X. . 1998 J. Biochem. 333: 645–654.
Hannon GJ, Demetrick D and Beach D. . 1993 Genes Dev. 7: 2378–2391.
Hansen K, Lukas J, Holm K, Kjerulff AA and Bartek J. . 1999 Electrophoresis 20: 372–381.
Harlow E, Whyte P, Franza Jr BR and Schley C. . 1986 Mol. Cell. Biol. 6: 1579–1589.
Helin K, Holm K, Niebuhr A, Eiberg H, Tommerup N, Hougaard S, Poulsen HS, Spang-Thomsen M and Norgaard P. . 1997 Proc. Natl. Acad. Sci. USA 94: 6933–6938.
Herzinger T, Wolf DA, Eick D and Kind P. . 1995 Oncogene 10: 2079–2084.
Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI and Weinberg RA. . 1992 Cell 70: 993–1006.
Hoshikawa Y, Mori A, Amimoto K, Iwabe K and Hatakeyama M. . 1998 Proc. Natl. Acad. Sci. USA 95: 8574–8579.
Hurford Jr RK, Cobrinik D, Lee MH and Dyson N. . 1997 Genes Dev. 11: 1447–1463.
Kitagawa M, Higashi H, Jung H-K, Tamai K, Kato J-Y, Segawa K, Yoshida E, Nishimura S and Taya Y. . 1996 EMBO J. 15: 7060–7069.
Koff A, Ohtsuki M, Polyak K, Roberts JM and Massagué J. . 1993 Science 260: 536–539.
Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin Jr WG, Seto E and Branton PE. . 1999a Mol. Cell. Biol. 19: 6632–6641.
Lai A, Marcellus RC, Corbeil HB and Branton PE. . 1999b Oncogene 18: 2091–2100.
Lee JO, Russo AA and Pavletich NP. . 1998 Nature 391: 859–865.
LeRoy G, Orphanides G, Lane WS and Reinberg D. . 1998 Science 282: 1900–1904.
Li Y, Graham C, Lacy S, Duncan AMV and Whyte P. . 1993 Genes Dev. 7: 2366–2377.
Lundberg AS and Weinberg RA. . 1998 Mol. Cell. Biol. 18: 753–761.
Mayol X, Garriga J and Graña X. . 1995 Oncogene 11: 810–808.
Mayol X, Garriga J and Graña X. . 1996 Oncogene 13: 237–246.
Mayol X, Graña X, Baldi A, Sang N, Hu Q and Giordano A. . 1993 Oncogene 8: 2561–2566.
Meloni AR, Smith EJ and Nevins JR. . 1999 Proc. Natl. Acad. Sci. USA 96: 9574–9579.
Moberg K, Starz MA and Lees JA. . 1996 Mol. Cell. Biol. 16: 1436–1449.
Pollack IF, Randall MS, Kristofik MP, Kelly RH, Selker RG and Vertosick FT. . 1990 J. Neurol. 73: 106–112.
Robanus-Maandag E, Dekker M, van der Valk M, Carrozza ML, Jeanny JC, Dannenberg JH, Berns A and te Riele H. . 1998 Genes Dev. 12: 1599–1609.
Schluter C, Duchrow M, Wohlenberg C, Becker MH, Key G, Flad HD and Gerdes J. . 1993 J. Cell. Biol. 123: 513–522.
Shew JY, Lin BT, Chen PL, Tseng BY, Yang-Feng TL and Lee WH. . 1990 Proc. Natl. Acad. Sci. USA 87: 6–10.
Smith EJ, Leone G, DeGregori J, Jakoi L and Nevins JR. . 1996 Mol. Cell. Biol. 16: 6965–6976.
Starborg M, Gell K, Brundell E and Hoog C. . 1996 J. Cell. Sci. 109: 143–153.
Stein GH. . 1979 J. Cell. Physiol. 99: 43–54.
Stubdal H, Zalvide J, Campbell KS, Schweitzer C, Roberts TM and DeCaprio JA. . 1997 Mol. Cell. Biol. 17: 4979–4990.
Tevosian SG, Shih HH, Mendelson KG, Sheppard KA, Paulson KE and Yee AS. . 1997 Genes Dev. 11: 383–396.
Thomas NS, Pizzey AR, Tiwari S, Williams CD and Yang J. . 1998 J. Biol. Chem. 273: 23659–23667.
Vairo G, Livingston DM and Ginsberg D. . 1995 Genes Dev. 9: 869–881.
van der Geer P and Hunter T. . 1994 Electrophoresis 15: 544–554.
Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA and Harlow E. . 1988 Nature 334: 124–129.
Wilm M, Shevchenko A, Houthaeve T, Breit S, Schweigerer L, Fotsis T and Mann M. . 1996 Nature 379: 466–469.
Wolf DA, Hermeking H, Albert T, Herzinger T, Kind P and Eick D. . 1995 Oncogene 10: 2067–2078.
Xiao ZX, Ginsberg D, Ewen M and Livingston DM. . 1996 Proc. Natl. Acad. Sci. USA 93: 4633–4637.
Zalvide J and DeCaprio JA. . 1995 Mol. Cell. Biol. 15: 5800–5810.
Zalvide J, Stubdal H and DeCaprio JA. . 1998 Mol. Cell. Biol. 18: 1408–1415.
Zhu L, van den Heuval S, Helin K, Fattaey A, Ewen M, Livingston DM, Dyson N and Harlow E. . 1993 Genes Dev. 7: 1111–1125.
Acknowledgements
We gratefully acknowledge the work of William S Lane in the Harvard Microchemistry Facility. pcDNA1-HAp130 was generously provided by Gino Vairo and HA-Δ21 by Juan Zalvide. AJ Canhoto was supported by NIH Training Grants 5T32CA09031 and 2T32CA09361. JA DeCaprio is a Scholar of the Leukemia and Lymphoma Society. This work was supported in part by Public Health Service grant RO1-CA63113 and a grant from Novartis Pharmaceuticals.
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Canhoto, A., Chestukhin, A., Litovchick, L. et al. Phosphorylation of the retinoblastoma-related protein p130 in growth-arrested cells. Oncogene 19, 5116–5122 (2000). https://doi.org/10.1038/sj.onc.1203893
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DOI: https://doi.org/10.1038/sj.onc.1203893
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