Poly(rC)-Binding Protein 2 Regulates Hippo Signaling To Control Growth in Breast Epithelial Cells
Autor: | Caroline C. Philpott, James A. Wohlschlegel, Ajay A. Vashisht, Kimberly Z. Bullough, Fengmin Li |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Scaffold protein Cytoplasm MST1 MAP Kinase Signaling System medicine.medical_treatment Protein Serine-Threonine Kinases Biology Cell Line Mice 03 medical and health sciences Mammary Glands Animal medicine Animals Humans Hippo Signaling Pathway Mammary Glands Human Molecular Biology Transcription factor Cell Proliferation Cell Nucleus Hippo signaling pathway Cell growth Growth factor RNA-Binding Proteins Epithelial Cells Articles Cell Biology Cell biology 030104 developmental biology Hippo signaling Phosphorylation Female Transcription Factors |
Zdroj: | Molecular and Cellular Biology. 36:2121-2131 |
ISSN: | 1098-5549 |
Popis: | 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. |
Databáze: | OpenAIRE |
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