Regulation of transcription factor ATF2 by the JNK/p38 signal transduction pathway is facilitated by interaction with retinoblastoma protein

Author

Huo Li

Date of Award

12-2000

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Wesley D. Wicks

Committee Members

John Koontz, Ranjan Ganguly, Naima Moustaid Moussa

Abstract

Two highly related transcription factors, ATF2 and ATFa, enhance the activity of the Transforming Growth Factor β2 (TGF-β2) 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. Whereas Mitogen-activated protein Kinase Kinase 7 (MKK7) or cJun N-terminal protein Kinase (JNK) expression enhances the actions of both ATF's, MKK6 or p38 expression only augments the effects of ATF2. Immunoprecipitation of lysates from transfected cells with Rb antibodies brings down expressed ATF2 but not ATFa. Expressed JNK and p38 are also immunoprecipitated in the same complex. Similarly, ATF2 antibodies bring down expressed Rb, JNK and p38. 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. This suggestion has been validated by direct measurements of the phosphorylation status of ATF2. cJun co-expression substantially enhances the actions of ATF2, but has no significant effects on the actions of ATFa. These results were also confirmed by the inhibition of the actions of ATF2 but not those of ATFa by a dominant negative mutant of cJun. cFos has no significant effects on either ATF. Regulation of endogenous TGF-β2 gene expression in PC-3 cells is highly correlated to that of the transfected TGF-β2 promoter construct, indicating the physiological relevance of studies with the TGF-β2 promoter.

Recommended Citation

Li, Huo, "Regulation of transcription factor ATF2 by the JNK/p38 signal transduction pathway is facilitated by interaction with retinoblastoma protein. " PhD diss., University of Tennessee, 2000.
https://trace.tennessee.edu/utk_graddiss/8336