Abstract
PARP is a multifunctional protein that can affect genome stability, transcription control, telomere length and cell death. Recently we have reported that PARP binds to and enhances B-MYB transactivating potential. B-MYB is a potentially oncogenic transcription factor involved in mammalian cell proliferation, survival and differentiation. B-MYB gene expression is growth regulated and B-MYB protein is phosphorylated during S phase by cyclin A or E/cdk2 kinase, resulting in augmented transactivating potential. Here we show that PARP induces phosphorylation of B-MYB protein at cdk2 phosphorylation sites, since a B-MYB protein with mutated cdk2 phosphorylation sites is refractory to PARP-induced phosphorylation and co-activation in mammalian cells. We propose that PARP functions as a B-MYB co-factor by promoting cyclin/cdk2-dependent B-MYB phosphorylation. These results highlight a novel role for PARP as a factor that integrates cyclin-dependent kinases signaling with gene transcription.
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References
Ansieau S, Kowentz-Leutz E, Dechend R, Leutz A . 1997 J. Mol. Med. 75: 815–819
Arsura M, Introna M, Passerini F, Mantovani A, Golay J . 1992 Blood 79: 2708–2716
Cervellera M, Raschella G, Santilli G, Tanno B, Ventura A, Mancini C, Sevignani C, Calabretta B, Sala A . 2000 J. Biol. Chem. 275: 21055–21060
Cervellera MN, Sala A . 2000 J. Biol. Chem. 275: 10692–10696
Damours D, Desnoyers S, D'Silva I, Poirier G . 1999 Biochem. J. 342: 249–268
Dignam JD, Lebovitz RM, Roeder RG . 1983 Nucleic Acids Res. 11: 1475–1489
Graf T . 1992 Curr. Opin. Genet. Dev. 2: 249–255
Hurford RK, Cobrinik D, Lee M-H, Dyson N . 1997 Genes Dev. 11: 1447–1463
Johnson TK, Schweppe RE, Septer J, Lewis RE . 1999 J. Biol. Chem. 274: 36741–36749
Kannan P, Yu Y, Wankhade S, Tainsky MA . 1999 Nucleic Acids Res. 27: 866–874
Kim T, Jung H, Min S, Kim KT, Ha H . 1999 FEBS Lett. 460: 363–368
Lam EW-F, Watson RJ . 1993 EMBO J. 12: 2705–2713
Lam EW-F, Robinson C, Watson RJ . 1992 Oncogene 7: 1885–1890
Lane S, Farlie P, Watson RJ . 1997 Oncogene 14: 2445–2453
Lin D, Fiscella M, O'Connor PM, Jackman J, Chen M, Luo LL, Sala A, Travali S, Apella E, Mercer WE . 1994 Proc. Natl. Acad. Sci. USA 91: 10079–10083
Malanga M, Pleschke JM, Kleczkowska HE, Althaus FR . 1998 J. Biol. Chem. 273: 11839–11843
Menegazzi M, Scarpa A, Carcereri de Prati A, Menestrina F, Suzuki H . 1999 Mol. Carcinog. 4: 256–261
Miyamoto T, Kakizawa T, Hashizume K . 1999 Mol. Cell. Biol. 19: 2644–2649
Nomura N, Takahashi M, Matsui M, Ishii S, Date T, Sasamoto S, Ishizaki R . 1988 Nucleic Acids Res. 16: 11075–11089
Plaza S, Aumercier M, Bailly M, Dozier C, Saule S . 1999 Oncogene 18: 1041–1051
Raschellá G, Cesi V, Amendola R, Negroni A, Tanno B, Altavista P, Tonini GP, DeBernardi B, Calabretta B . 1999 Cancer Res. 59: 3365–3368
Raschellá G, Negroni A, Sala A, Pucci S, Romeo A, Calabretta B . 1995 J. Biol. Chem. 270: 8540–8545
Reiss K, Travali S, Calabretta B, Baserga R . 1991 J. Cell. Physiol. 148: 338–343
Robinson C, Light Y, Groves R, Mann D, Marias R, Watson R . 1996 Oncogene 12: 1855–1864
Sala A, Saitta B, De Luca P, Cervellera MN, Casella I, Lewis RE, Watson R, Peschle C . 1999 Oncogene 18: 1333–1339
Sala A, Watson R . 1999 J. Cell. Physiol. 179: 245–250
Sala A, Calabretta B . 1992 Proc. Natl. Acad. Sci. USA 89: 10415–10419
Sala A, Casella I, Bellon T, Calabretta B, Watson RJ, Peschle C . 1996 J. Biol. Chem. 271: 9363–9367
Sala A, Kundu M, Casella I, Engelhard A, Calabretta B, Grasso L, Paggi MG, Giordano A, Watson RJ, Khalil K, Peschle C . 1997 Proc. Natl. Acad. Sci. USA 94: 532–536
Saville MK, Watson RJ . 1998 Adv. Cancer Res. 72: 109–140
Simbulan-Rosenthal CM, Ly DH, Rosenthal DS, Konopka G, Luo R, Wang ZQ, Schultz PG, Smulson ME . 2000 Proc. Natl. Acad. Sci. USA 97: 11274–11279
Simbulan-Rosenthal CM, Rosenthal DS, Hilz H, Hickey R, Malkas L, Applegren N, Wu Y, Bers G, Smulson . 1996 Biochemistry 35: 11622–11633
Soldatenkov VA, Albor A, Patel BK, Dreszer R, Dritschilo A, Notario V . 1999 Oncogene 18: 3954–3962
Tanaka Y, Patestos NP, Maekawa T, Ishii . 1999 J. Biol. Chem. 274: 28067–28070
Ziebold U, Bartsch O, Marais R, Ferrari S, Klempnauer KH . 1997 Curr. Biol. 7: 253–260
Zwicker J, Liu N, Engeland K, Lucibello FC, Muller R . 1996 Science 271: 1595–1597
Acknowledgements
Giorgia Santilli is a recipient of a fellowship from the Fondazione Italiana per la Ricerca sul Cancro (FIRC). This work was supported in part by a grant from the Italian Ministry of Health (Progetto finalizzato Ministero della Sanita'). Danilo Perrotti and Bruno Calabretta are gratefully acknowledged for support and critical reading of the manuscript.
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Santilli, G., Cervellera, M., Johnson, T. et al. PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites. Oncogene 20, 8167–8174 (2001). https://doi.org/10.1038/sj.onc.1204943
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DOI: https://doi.org/10.1038/sj.onc.1204943
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