Retinoblastoma protein interacts with ATF2 and JNK/p38 in stimulating the transforming growth factor-beta2 promoter.
Two highly related transcription factors, ATF2 and ATFa, enhance the activity of the Transforming Growth Factor beta2 (TGF-beta2) promoter via a partial cAMP response element in transfected CHO cells. The retinoblastoma protein (Rb) also activates this promoter and enhances the stimulatory effects of ATF2 but causes near extinction of the effects of ATFa. The site on Rb required for its effects alone and in combination with the ATFs has been mapped mainly to the A/B pockets but the C pocket is also implicated. Whereas MKK7 or JNK expression enhances the actions of both ATFs, MKK6 or p38 expression only augments the effects of ATF2. Immunoprecipitation with Rb antibodies of lysates from transfected cells brings down expressed ATF2 but not ATFa. Expressed JNK and p38 are also found in the anti-Rb immunoprecipitates. ATF2 antibodies bring down expressed Rb, JNK and p38 and expression of Rb enhances the immunoprecipitation of both JNK and p38 by ATF2 antibodies. The results suggest that Rb is acting as a matchmaker by bridging either JNK or p38 with their common substrate ATF2 and, hence, facilitating its activation. Consistent with this suggestion, expression of Rb enhances the phosphorylation of ATF2 in CHO cells.
Li
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Department of Biochemistry, University of Tennessee, Knoxville, Tennessee 37996-0840, USA.
Wicks
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WD
D051698:Activating Transcription Factor 2; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; D048688:MAP Kinase Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053781:Transforming Growth Factor beta2; D048051:p38 Mitogen-Activated Protein Kinases
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; D048688:MAP Kinase Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases