title: Poly(rC)-Binding Protein 2 Regulates Hippo Signaling To Control Growth in Breast Epithelial Cells.
abstract: Poly(rC)-binding proteins (PCBPs) are multifunctional adapters that mediate interactions between nucleic acids, iron cofactors, and other proteins, affecting the fates and activities of the components of these interactions. Here, we show that PCBP2 forms a complex with the Hippo pathway components Salvador (Sav1), Mst1, Mst2, and Lats1 in human cells and mouse tissues. Hippo is a kinase cascade that functions to phosphorylate and inactivate the transcriptional coactivators YAP and TAZ, which control cell growth and proliferation. PCBP2 specifically interacts with the scaffold protein Sav1 and prevents proteolytic cleavage of the Mst1 kinase, resulting in increased signaling through Hippo and suppressed activity of YAP and TAZ. Human breast epithelial cells lacking PCBP2 exhibit impaired proteasomal degradation of TAZ. They accumulate TAZ in both the nucleus and the cytosol, increase expression of YAP and TAZ connective tissue growth factor (CTGF) and Cyr61 target genes, and exhibit anchorage-independent growth. Thus, PCBP2 can function as a component of the Hippo complex, enhancing signaling, suppressing activity of YAP and TAZ, and altering the growth characteristics of cells.
authors.affiliation: Genetics and Metabolism Section, Liver Disease Branch, NIDDK, NIH, Bethesda, Maryland, USA.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Li
authors.affiliation: Genetics and Metabolism Section, Liver Disease Branch, NIDDK, NIH, Bethesda, Maryland, USA.
authors.forename: Kimberly Z
authors.initials: KZ
authors.lastname: Bullough
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.affiliation: Genetics and Metabolism Section, Liver Disease Branch, NIDDK, NIH, Bethesda, Maryland, USA carolinep@mail.nih.gov.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Philpott
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells; D005260:Female; D000090683:Hippo Signaling Pathway; D006801:Humans; D020935:MAP Kinase Signaling System; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C501903:PCBP2 protein, human; C501904:Pcbp2 protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases