title: 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.
authors.affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstr. 11, 07745 Jena, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lindner
authors.forename: Pavel
authors.initials: P
authors.lastname: Urbánek
authors.forename: Birgit
authors.initials: B
authors.lastname: Pavelka
authors.forename: Monika
authors.initials: M
authors.lastname: Hartmann
authors.forename: Peter
authors.initials: P
authors.lastname: Herrlich
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D051379:Mice; D041681:NIH 3T3 Cells; D010703:Phorbol Esters / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012313:RNA / Q000737:chemistry; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018960:Hyaluronan Receptors; D010703:Phorbol Esters; D012313:RNA; D018631:ras Proteins
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