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Transforming growth factor‐β regulation of retinoblastoma gene product and E2F transcription factor during cell cycle progression in mouse fibroblasts
Author(s) -
Kim TaeAug,
Ravitz Michael J.,
Wenner Charles E.
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041600102
Subject(s) - e2f , biology , transforming growth factor , cell cycle , transcription factor , phosphorylation , transforming growth factor beta , epidermal growth factor , hyperphosphorylation , retinoblastoma protein , microbiology and biotechnology , cancer research , gene , cell culture , genetics
The mechanism by which transforming growth factor beta (TGFβ) exerts growth stimulatory effects was examined in C3H/10T1/2 mouse fibroblasts by study of cell cycle regulation of the retinoblastoma gene product (p110 Rb ) and transcriptional regulation of the p110 Rb ‐associated transcription factor, E2F. Northern blotting analysis shows that TGFβ and/or epidermal growth factor (EGF) stimulate by three to sixfold the level of Rb mRNA which is also reflected by the increased levels of p110 Rb . p110 Rb becomes phosphorylated in mid‐G1 and further phosphorylated at the G 1 /S transition. Hyperphosphorylation of p110 Rb by TGFβ can be observed when cells are in S phase. TGFβ stimulates by three to fourfold the activity of cdk2 kinase consistent with the observed phosphorylation of p110 Rb and also with the possibilit that the kinase is involved in phosphorylating p110 Rb close to the G 1 /S transition. Thus, TGFβ as a growth stimulator induces, as does EGF, the phosphorylation of p110 Rb during cell cycle progression. Transient transfection of E2F promoter constructs was used to analyze the effect of TGFβ on the modulation of E2F‐mediated transcription. The data revealed that TGFβ can stimulate wild‐type adenoviral E2 promoter activity by 12‐fold. Taken together, TGFβ‐induced phosphorylation of p110 Rb in mouse fibroblasts appears to exert a positive regulatory function upon genes that have a pivotal role in the G 1 /S transition of the cell cycle. © 1994 Wiley‐Liss, Inc.