HTML версия книгиThe promyelocytic Страница 1
Чтобы смотреть книгу во Flash, необходим Flash Player 8 или старше, а также Javascript должен быть включен. Скачать Flash Player можно здесь

The promyelocytic leukaemia protein tumour suppressor functions as a transcriptional regulator of p63


Francesca Bernassola, Andrew Oberst, Gerry Melino and Pier Paolo Pandolfi

Oncogene (2005) 24, 6982–6986



p63 plays unique developmental roles in epidermal morphogenesis, despite its structural similarity with p53. The p63 gene has two distinct promoters, coding for proteins containing an N-terminal transactivation domain (TAisoform s) and for proteins lacking this region (DN isoforms). The full-length transcriptionally active TAp63 isoforms are capable of transactivating the majority of the p53 target promoters thus inducing cell cycle arrest and apoptosis. On the contrary, the DNp63 isoforms seem to counteract the transactivation activities of p53 and TAp63 proteins, thus possibly conferring a proliferative advantage to cancer cells. However, the molecular mechanisms controlling the transcriptional activity of p63 remain largely unclear. Here we present data indicating that (i) the promyelocytic leukaemia protein (PML) physically interacts with p63, (ii) p63 is localized into the PML nuclear-bodies (PML-NBs) in vivo, and (iii) PML regulates p63 transcriptional activity. We show that the interaction of p63 with PML increases the levels of p63 in cultured cells as well as its ability to transactivate the p53-responsive elements of the GADD45, p21 and bax promoters. These data are consistent with a general role for PML as a functional modulator of all the p53 family members. Our findings strengthen the relevance of the cross talk between PML and the p53 family members, imply a new tumour suppressive function of PML and unveil a possible role for PML in epidermal morphogenesis and differentiation.


Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH and Pandolfi PP. (2004). Nat. Cell. Biol., 6, 665–672.

Bernassola F, Salomoni P, Oberst A, Di Como CJ, Pagano M, Melino G and Pandolfi PP. (2004). J. Exp. Med., 199, 1545–1557.

Crook T, Nicholls JM, Brooks L, O’Nions J and Allday MJ. (2000). Oncogene, 19, 3439–3444.

de The H, Lavau C, Marchio A, Chomienne C, Degos L and Dejean A. (1991). Cell, 66, 675–684.

Dignam JD, Lebovitz RM and Roeder RG. (1983). Nucleic Acids Res., 11, 1475–1489.

Duijf PH, Vanmolkot KR, Propping P, Friedl W, Krieger E, McKeon F, Dotsch V, Brunner HG and van Bokhoven H. (2002). Hum. Mol. Genet., 11, 799–804.

Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C and Lowe SW. (2000). Genes Dev., 14, 2015–2027.

Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C and Del Sal G. (2000). EMBO J., 19, 6185–6195.

Goddard AD, Borrow PS, Freemont PS and Solomon E. (1991). Science, 254, 1371–1374.

Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W and Pandolfi P. (2000). Nat. Cell. Biol., 2, 730–736.

Gurrieri C, Capodieci P, Bernardi R, Scaglioni PP, Nafa K, Rush LJ, Verbel DA, Cordon-Cardo C and Pandolfi PP. (2004). J. Natl. Cancer Inst., 96, 269–279.

Melino G, De Laurenzi V and Vousden KH. (2002). Nat. Rev. Cancer, 2, 605–615.

Melino G, Lu X, Gasco M, Crook T and Knight RA. (2003). Trends Biochem. Sci., 28, 663–670.

Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR and Bradley A. (1999). Nature, 398, 708–713.

Nylander K, Vojtesek B, Nenutil R, Lindgren B, Roos G, Zhanxiang W, Sjostrom B, Dahlqvist A and Coates PJ. (2002). J. Pathol., 198, 417–427.

Pandolfi PP, Grignani F, Alcalay M, Mencarelli A, Biondi A, LoCoco F and Pelicci PG. (1991). Oncogene, 6, 1285–1292.

Park BJ, Lee SJ, Kim JI, Lee CH, Chang SG, Park JH and Chi SG. (2000). Cancer Res., 60, 3370–3374.

Parsa R, Yang A, McKeon F and Green H. (1999). J. Invest. Dermatol., 113, 1099–1105.

Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP and Pelicci PG. (2000). Nature, 406, 207–210.

Piazza F, Gurrieri C and Pandolfi PP. (2001). Oncogene, 20, 7216–7222.

Salomoni P and Pandolfi PP. (2002). Cell, 108, 165–170.

Urist MJ, Di Como CJ, Lu ML, Charytonowicz E, Verbel D, Crum CP, Ince TA, McKeon FD and Cordon-Cardo C. (2002). Am. J. Pathol., 161, 1199–1206.

Weber A, Bellmann U, Bootz F, Wittekind C and Tannapfel A. (2002a). Int. J. Cancer, 99, 22–28.

Weber A, Langhanki L, Schutz A, Gerstner A, Bootz F, Wittekind C and Tannapfel A. (2002b). Virchows Arch., 441, 428–436.

Westfall MD, Mays DJ, Sniezek JC and Pietenpol JA. (2003). Mol. Cell. Biol., 23, 2264–2276.

Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CC, Dong SM, Guo Z, Benoit N, Cohen Y, Rechthand P, Califano J, Moon CS, Ratovitski E, Jen J, Sidransky D and Trink B. (2003). Cancer Res., 63, 2351–2357.

Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D and McKeon F. (1998). Mol. Cell, 2, 305–316.

Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C and McKeon F. (1999). Nature, 398, 714–718.

Zhong S, Salomoni P and Pandolfi PP. (2000). Nat. Cell. Biol., 2, E85–90.