2794

Previously, the ING2/ING1L gene, ING2a, was identified as a candidate tumor suppressor gene encoding a protein that modulates p53. Here we identified a novel splice variant of the gene that is transcribed from a different promoter that is located in intron 1 of the ING2a gene. Because both ING2a and ING2b are composed of two exons and share exon 2, only the N-terminal region encoded by a different exon 1 is different. Although we observed that both ING2a and ING2b inhibited cell growth by colony formation assay, only ING2a induced p21 promoter activity, and ING2b competed with this effect, suggesting that ING2b may have a dominant negative effect on ING2a. We also found that ING2a binds to mSin3A more strongly than ING2b; on the other hand ING2b binds to Brg1 more strongly than ING2a, suggesting that the major roles of ING2a and ING2b may be slightly different. Because the effect of ING2a and ING2b on cell growth is almost the same, the splice variants might compensate or promote each other’s function.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA