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PMID: 9710627 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Id2 promotes apoptosis by a novel mechanism independent of dimerization to basic helix-loop-helix factors.

Molecular and cellular biology ·Vol. 18 ·No. 9 ·1998-09-00 ·Pages 5435-44

Florio M, Hernandez MC, Yang H, Shu HK, Cleveland JL, Israel MA

Abstract

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.

MeSH Terms
Animals Apoptosis Bone Marrow Cells Cell Line Cell Survival DNA-Binding Proteins/biosynthesis,chemistry,metabolism Dimerization Gene Expression Regulation/drug effects Helix-Loop-Helix Motifs Inhibitor of Differentiation Protein 2 Interleukin-3/pharmacology Kinetics Mice Recombinant Proteins/biosynthesis,chemistry,metabolism Repressor Proteins Time Factors Transcription Factors Transfection
Chemicals
DNA-Binding Proteins Idb2 protein, mouse Inhibitor of Differentiation Protein 2 Interleukin-3 Recombinant Proteins Repressor Proteins Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Florio M
Preuss Laboratory for Molecular Neuro-Oncology, Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California 94143-0520, USA.
Hernandez M C
Yang H
Shu H K
Cleveland J L
Israel M A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.9.5435
Published
1998-09-00
Pages
5435-44
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109128
Subset
IM
Grants
NCI NIH HHS · CA76379 · United States
NCI NIH HHS · CA21765 · United States
NCI NIH HHS · CA13525 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.9.5435 PMC Full Text View journal details
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