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Background   CDKN2A/p16   INK4a   is frequently altered in human cancers and it is the most important melanoma susceptibility gene identified to date. p16 INK4a  inhibits pRb phosphorylation and induces cell cycle arrest, which is considered its main tumour suppressor function. Nevertheless, additional activities may contribute to the tumour suppressor role of p16 INK4a  and could help explain its specific association with melanoma predisposition. To identify such functions we conducted a yeast-two-hybrid screen for novel p16 INK4a  binding partners.    Results  We now report that p16 INK4a  interacts with the chromatin remodelling factor BRG1. We investigated the cooperative roles of p16 INK4a  and BRG1 using a panel of cell lines and a melanoma cell model with inducible p16 INK4a  expression and BRG1 silencing. We found evidence that BRG1 is not required for p16 INK4a -induced cell cycle inhibition and propose that the p16 INK4a -BRG1 complex regulates BRG1 chromatin remodelling activity. Importantly, we found frequent loss of BRG1 expression in primary and metastatic melanomas, implicating this novel p16 INK4a  binding partner as an important tumour suppressor in melanoma.    Conclusion  This data adds to the increasing evidence implicating the SWI/SNF chromatin remodelling complex in tumour development and the association of p16 INK4a  with chromatin remodelling highlights potentially new functions that may be important in melanoma predisposition and chemoresistance.

The chromatin remodelling factor BRG1 is a novel binding partner of the tumor suppressor p16INK4a