Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex

The candidate tumor suppressor ING1 was identified in a genetic screen aime d at isolation of human genes whose expression is suppressed in cancer cell s. It may function as a negative growth regulator in the p53 signal transdu ction pathway. However, its molecular mechanism is not clear. The ING1 locu s encodes alternative transcripts of p47(ING1a), P33(ING1b) and p24(ING1c). Here we report differential association of protein products of ING1 with t he mSin3 transcriptional corepressor complex. p33(ING1b) associates with Si n3, SAP30, HDAC1, RbAp48, and other proteins, to form large protein complex es, whereas p24(ING1c) does not. The ING1 immune complexes are active in de acetylating core histones in vitro, and p33(ING1b) is functionally associat ed with HDAC-1-mediated transcriptional repression in transfected cells, Ou r data provide basis for a p33(ING1b)-specific molecular mechanism for the function of the ING1 locus.