The growth-inhibitory block of TGF-beta is located close to the G1/S border in the cell cycle.
Transforming growth factor-beta (TGF-beta) inhibits DNA synthesis in dense cultures of young human embryonic fibroblasts and antagonizes the mitogenic action of platelet-derived growth factor (PDGF). The inhibition of the PDGF-BB action by TGF-beta was independent of the induction of mRNAs for the PDGF-A chain and PDGF-beta receptor, the predominant types of PDGF receptor in human fibroblasts. The TGF-beta-mediated inhibition did not influence the expression of various genes that are involved in the transition from the arrested (GO) state to the S phase of the cell cycle. Indeed, TGF-beta upregulated the "early" genes c-myc, c-fos, and junB and downregulated the growth arrest-specific (gas) genes. These results suggest that the inhibition of DNA synthesis by TGF-beta in human fibroblasts is independent of modulation of expression of early and gas genes, placing the TGF-beta block comparatively late in the GO to S transition. In cultures of senescent human fibroblasts TGF-beta stimulated DNA synthesis but, nevertheless, had the same effect as in young cells on the expression of PDGF chains and receptor genes, as well as on early and gas genes, with the exception of a significantly lower induction of c-fos.
Kletsas
D
D
Institute of Biology, N.C.S.R. Demokritos, Athens, Greece.
Stathakos
D
D
Sorrentino
V
V
Philipson
L
L
D018797:Cell Cycle Proteins; D016922:Cellular Senescence; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase / Q000235:genetics / Q000502:physiology*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D017781:Genes, Immediate-Early; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D016212:Transforming Growth Factor beta / Q000502:physiology*; D000099255:Growth Arrest-Specific Protein 6
D018797:Cell Cycle Proteins; D004247:DNA; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor; D029701:Saccharomyces cerevisiae Proteins; D016212:Transforming Growth Factor beta; D000099255:Growth Arrest-Specific Protein 6; C066709:GAS1 protein, S cerevisiae; C096192:GAS1 protein, human