Role of Sp1 phosphorylation in mechanotranscriptional activation of filamin A.
Published: 2005
Language: eng
Number of pages: 82
Description: Connective tissue cells survive mechanical forces by inducing the expression of filamin A, an actin cross-linking protein that inhibits force-induced cell death. Filamin A expression is dependent on p38 activation and Sp-1 binding to the filamin promoter. Force application through integrins increased filamin promoter activity by >5-fold but was blocked by mutations to Sp1 binding sites in the filamin promoter. In Sp deficient SL2 cells, transfection with wild-type but not mutant Sp1 caused phosphorylation of Sp1 at both Thr453 and Thr739 and enhanced binding of nuclear extracts to a filamin promoter. Sp1 phosphorylated at Thr453 and Thr739 by p38 bound to filamin promoter more than unphosphorylated Sp1. Recombinant active p38 phosphorylated wild-type Sp1 but not the Sp1T453A-T739A double mutant protein in vitro. We conclude that filamin A expression is increased by p38-induced phosphorylation of Sp1 at specific threonine residues that in turn enhances binding to the filamin promoter.
Notes: Source: Masters Abstracts International, Volume: 44-02, page: 0806.

Thesis (M.Sc.)--University of Toronto, 2005.

Electronic version licensed for access by U. of T. users.

GERSTEIN MICROTEXT copy on microfiche (1 microfiche).