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


Authors: Bernassola, F.; Oberst, A.; Melino, G.; Pandolfi, P. P.
Article Title: The promyelocytic leukaemia protein tumour suppressor functions as a transcriptional regulator of p63
Abstract: 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 (TA isoforms) and for proteins lacking this region (ΔN 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 ΔNp63 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. © 2005 Nature Publishing Group. All rights reserved.
Keywords: controlled study; human cell; promoter region; dna-binding proteins; protein function; protein localization; protein protein interaction; neoplasm proteins; in vivo study; transcription, genetic; transcription factors; nuclear proteins; tumor suppressor gene; transcription regulation; cell culture; tumor suppressor proteins; transactivation; transcription; phosphoproteins; cellular distribution; protein p63; trans-activators; concentration (parameters); protein p21; genes, tumor suppressor; p63; promyelocytic leukemia protein; protein bax; pml; cell nucleus inclusion body; growth arrest and dna damage inducible protein 45; nuclear body
Journal Title: Oncogene
Volume: 24
Issue: 46
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2005-10-20
Start Page: 6982
End Page: 6986
Language: English
DOI: 10.1038/sj.onc.1208843
PUBMED: 16007146
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 25" - "Export Date: 24 October 2012" - "CODEN: ONCNE" - "Source: Scopus"
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  1. Andrew Oberst
    2 Oberst