Genotoxic-stress-response genes and growth-arrest genes. gadd, MyD, and other genes induced by treatments eliciting growth arrest.
As discussed throughout this paper, many mammalian DDI genes are associated with growth responses, including both positive responses to growth stimulation and negative responses involving transient growth arrest and terminal differentiation. It is interesting that several immediate-early genes encoding transcription factors, the jun genes, are DDI, are induced by terminal differentiation, and also are associated with positive growth responses. In negative growth-response genes, their control is complex and almost certainly involves multiple regulatory mechanisms. The role of growth-arrest genes after exposure to DNA-damaging agents is currently not known, but as growth arrest can have a protective effect on cells exposed to DNA-damaging agents in both bacteria and eukaryotes, some protective role(s) for the gadd genes may exist. Whatever the roles are for the individual gadd genes, the response of the gadd genes to DNA-damaging agents and other growth-arrest signals has been highly conserved during mammalian evolution, and it is likely that this stress response, as reflected by induction of one or more gadd genes, is present in most or perhaps all mammalian cells. Our findings that the gadd group overlaps with another group of growth-arrest genes, the MyD, indicate that these two groups combined define a new class of genes whose protein products are likely to play a role in cell growth cessation.
Fornace
A J
AJ
Laboratory of Molecular Pharmacology, D.T.P., N.C.I. National Institutes of Health Bethesda, Maryland 20892.
Jackman
J
J
Hollander
M C
MC
Hoffman-Liebermann
B
B
Liebermann
D A
DA
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D016466:CHO Cells; D002453:Cell Cycle; D006224:Cricetinae; D004249:DNA Damage; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP