A link between two tumorigenic proteins, CD44 and p21WAF1: CD44 increases phorbol ester-induced expression of p21WAF1 by stabilizing its mRNA and extending protein half-life

Abstract

The cell surface glycoprotein CD44 enhances phorbol-12-myristate 13-acetate (TPA)-induced expression of p21WAF1 by stabilizing its mRNA and enhancing the protein's half-life in several cell lines. Only the plasma membrane-anchored cytoplasmic tail of CD44 and its interacting ezrin, radixin, moesin (ERM) proteins are required for this effect. A mitogen activated kinase (MEK) inhibitor abolishes the action of CD44 on p21. Down-regulation of p21 dramatically decreased anchorage-independence of a cancer cell line, whereas CD44 expression in this background could partially rescue the phenotype.

Keywords: Agar colony formation; CD44; CD44KR-Mt and CD44KK-Mt; CHX; ERM; ERM proteins; Ez; FACS; ICD; KD; MAPK; MEK; PKC; RNA and protein stabilization; Ras/MAPK-pathway; TPA; V; control; ctrl; cycloheximide; deletion of extracellular domain; deletion of the intracellular domain; empty vector; ezrin; ezrin, radixin, moesin; fluorescence activated cell sorting; intracellular domain; knockdown; mitogen activated kinase; mitogen activated protein kinase; mutations of the ERM binding domain of CD44; p21; phorbol-12-myristate 13-acetate; protein kinase C; qRT-PCR; quantitative real-time PCR; ΔE; ΔICD.