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 aimed at isolation of human genes whose expression is suppressed in cancer cells. It may function as a negative growth regulator in the p53 signal transduction pathway. However, its molecular mechanism is not clear. The ING1 locus encodes alternative transcripts of p47^ING1a, p33 ^ING1b, and p24^ING1c. Here we report differential association of protein products of ING1 with the mSin3 transcriptional corepressor complex. p33^ING1b associates with Sin3, SAP30, HDAC1, RbAp48, and other proteins, to form large protein complexes, whereas p24 ^ING1c does not. The ING1 immune complexes are active in deacetylating core histones in vitro, and p33^ING1b is functionally associated with HDAC1-mediated transcriptional repression in transfected cells. Our data provide basis for a p33^ING1b-specific molecular mechanism for the function of the ING1 locus.