The Hsp70–Bag3 complex modulates the phosphorylation and nuclear translocation of Hippo pathway protein Yap
Autor: | Zhi-Xiong Jim Xiao, Simone Baldan, Anatoli B. Meriin, Michael Y. Sherman, Julia Yaglom, Xaralabos Varelas, Ilya Alexandrov |
---|---|
Rok vydání: | 2021 |
Předmět: |
YAP1
Hippo signaling pathway Kinase Cell Biology Biology Phosphoproteins Cell biology Proteotoxicity Proteasome Phosphorylation Hippo Signaling Pathway Signal transduction Nuclear localization sequence Adaptor Proteins Signal Transducing Cell Proliferation Signal Transduction Transcription Factors Research Article |
Zdroj: | J Cell Sci |
ISSN: | 1477-9137 0021-9533 |
Popis: | Protein abnormalities can accelerate aging causing protein misfolding diseases, and various adaptive responses have evolved to relieve proteotoxicity. To trigger these responses, cells must detect the buildup of aberrant proteins. Previously we demonstrated that the Hsp70–Bag3 (HB) complex senses the accumulation of defective ribosomal products, stimulating signaling pathway proteins, such as stress kinases or the Hippo pathway kinase LATS1. Here, we studied how Bag3 regulates the ability for LATS1 to regulate its key downstream target YAP (also known as YAP1). In naïve cells, Bag3 recruited a complex of LATS1, YAP and the scaffold AmotL2, which links LATS1 and YAP. Upon inhibition of the proteasome, AmotL2 dissociated from Bag3, which prevented phosphorylation of YAP by LATS1, and led to consequent nuclear YAP localization together with Bag3. Mutations in Bag3 that enhanced its translocation into nucleus also facilitated nuclear translocation of YAP. Interestingly, Bag3 also controlled YAP nuclear localization in response to cell density, indicating broader roles beyond proteotoxic signaling responses for Bag3 in the regulation of YAP. These data implicate Bag3 as a regulator of Hippo pathway signaling, and suggest mechanisms by which proteotoxic stress signals are propagated. |
Databáze: | OpenAIRE |
Externí odkaz: |