Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways

Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways

^*Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305; ^†Molecular Biology Program, Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and ^‡Howard Hughes Medical Institute and ^§Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104

Contributed by Roger D. Kornberg

Abstract

A multiprotein complex isolated from murine cells is identified as a counterpart of the yeast Mediator of transcriptional regulation on the basis of the following: homologs of two subunits of yeast Mediator, Srb7 and Med7, copurify with the complex; peptide sequencing reveals, in addition, homologs of the yeast Mediator subunits Rgr1 and Med6; as with yeast Mediator, the mouse complex binds to the RNA polymerase II C-terminal domain (CTD) and stimulates phosphorylation of the CTD by TFIIH. Peptide sequencing also identifies a component of mouse Mediator as a relative of Ring-3 protein, a mitogen-activated nuclear protein kinase, raising the possibility of Mediator as an end point of signal transduction pathways.

MED genes/SRB genes/Ring-3/C-terminal domain/TFIIH kinase

Footnotes

↵ ¶ To whom reprint requests should be addressed. e-mail: kornberg{at}cellbio.stanford.edu.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF031383).
ABBREVIATIONS:

CTD,

C-terminal domain;

EST,

expressed sequence tag;

GST,

glutathione S-transferase