Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta.
E proteins function in many developmental processes and are essential for the formation of lymphocyte progenitors. However, it is not known whether E proteins regulate lymphocyte survival, proliferation or differentiation or how their activity is regulated during lymphocyte development. We show here a role for Id3, an inhibitor of E protein activity, in the induction of apoptosis and growth arrest. Id3 is induced in response to transforming growth factor beta (TGF-beta), a pleiotropic cytokine that inhibits the growth and survival of normal and transformed lymphocyte progenitors. In the absence of Id3, the response of lymphocyte progenitors to TGF-beta is perturbed, which indicates that Id3 is a mediator of this response. Our data show a key role for E proteins in lymphocyte survival and link the activity of E proteins, and their antagonists, to members of the TGF-beta family of cytokines.
Kee
B L
BL
Department of Biology, University of California, San Diego, La Jolla 92093, USA. bkee@biomail.ucsd.edu
Rivera
R R
RR
Murre
C
C
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D051796:Inhibitor of Differentiation Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C407909:TCF3 protein, human; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; C075640:ID3 protein, human