ID2 PROMOTES APOPTOSIS BY A NOVEL MECHANISM INDEPENDENT OF DIMERIZATION TO BASIC HELIX-LOOP-HELIX FACTORS

Members of the helix-loop-helix (HLH) family of Id proteins have demon strated roles in the regulation of differentiation and cell proliferat ion. Id proteins inhibit differentiation by HLH-mediated heterodimeriz ation with basic HLH transcription factors. This blocks their sequence -specific binding to DNA and activation of target genes that are often expressed in a tissue-specific manner. Id proteins can also act as po sitive regulators of cell proliferation. The different mechanisms prop osed for Id-mediated promotion of entry into S phase also involve HLH- mediated interactions affecting regulators of the G(1)/S transition. W e have found that Id2 augments apoptosis in both interleukin3 (IL-3)-d ependent 32D.3 myeloid progenitors and U2OS osteosarcoma cells. We cou ld not detect a similar activity for Id3. In contrast to the effects o f Id2 on differentiation and cell proliferation, Id2-mediated apoptosi s is independent of HLH-mediated dimerization. The ability of Id2 to p romote cell death resides in its N-terminal region and is associated w ith the enhanced expression of a known component of the programmed cel l death pathway, the proapoptotic gene BAX.