Differential regulation of transcription of p21 and cyclin D1 conferred by TAF(II)250.
The TATA-binding protein-associated factor TAF(II)250, the largest subunit of TFIID, was first identified as the cell cycle regulatory protein CCG1. The ts13 Syrian hamster ovary fibroblast cell line, which contains a temperature-sensitive point mutation in TAF(II)250/CCG1, is arrested in G1 following a shift to the nonpermissive temperature. Here we demonstrate that the level of the D-type cyclins, in particular D1, was reduced, whereas the level of the cyclin-dependent kinase inhibitor p21 was stimulated in ts13 cells at the nonpermissive temperature. The levels of expression of cyclins A and E were not affected by temperature shift. We further show that at least part of the regulation of D1 and p21 levels in ts13 cells is mediated at the level of transcription initiation. These results suggest that the effect of the temperature-sensitive mutation TAF(II)250 on cell growth can be mediated through the differential regulation of transcription of specific cell growth regulatory genes, such as cyclin D1 and p21.
Rushton
J J
JJ
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pennsylvania 15261, USA.
Steinman
R A
RA
Robbins
P D
PD
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D006224:Cricetinae; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D056743:Cyclin D3; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D035381:TATA-Binding Protein Associated Factors; D013696:Temperature; D035362:Transcription Factor TFIID; D014158:Transcription, Genetic; D014162:Transfection
D019925:Cyclin A; D056743:Cyclin D3; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D019938:Cyclin D1; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa