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 demonstrated roles in the regulation of differentiation and cell proliferation. Id proteins inhibit differentiation by HLH-mediated heterodimerization 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 positive regulators of cell proliferation. The different mechanisms proposed for Id-mediated promotion of entry into S phase also involve HLH-mediated interactions affecting regulators of the G1/S transition. We have found that Id2 augments apoptosis in both interleukin-3 (IL-3)-dependent 32D.3 myeloid progenitors and U2OS osteosarcoma cells. We could not detect a similar activity for Id3. In contrast to the effects of Id2 on differentiation and cell proliferation, Id2-mediated apoptosis is independent of HLH-mediated dimerization. The ability of Id2 to promote cell death resides in its N-terminal region and is associated with the enhanced expression of a known component of the programmed cell death pathway, the proapoptotic gene BAX.
Preuss Laboratory for Molecular Neuro-Oncology, Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California 94143-0520, USA.
M
M
Florio
M C
MC
Hernandez
H
H
Yang
H K
HK
Shu
J L
JL
Cleveland
M A
MA
Israel
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells; D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects; D018257:Helix-Loop-Helix Motifs; D051797:Inhibitor of Differentiation Protein 2; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection
D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D007377:Interleukin-3; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors