Hsp70/Hsp90 organizing protein (HOP) maintains CRAF kinase activity and regulates MAPK signaling by enhancing Hsp90-CRAF association
Gayen, N.; Mitra, S.; Roy, S.; Mandal, A. K.
Show abstract
The stability and activity of CRAF kinase are stringently regulated by heat shock protein 90 (Hsp90). Hsp90-mediated client folding and maturation is governed by its co-chaperones, but their functionality in chaperoning CRAF/Raf1 kinase to accomplish signaling under physiological conditions remains poorly understood. Here, we show that Hsp70/Hsp90 organizing protein (HOP) associates with CRAF kinase for maintaining its kinase activity and facilitates the activation of the MAPK pathway. Such activation is mediated by TPR2A-2B-DP2 domain of HOP and requires efficient binding to Hsp90. Being a recruiter of Hsp90, Cdc37 is unable to supplement the function of HOP/Sti1. Downregulation of HOP/Sti1 in yeast and in vitro cell culture significantly reduces the CRAF signaling. Our data suggest that Hsp90 is recruited to CRAF in two steps, separately initiated by co-chaperones HOP and Cdc37 respectively during CRAF folding/maturation, and again upon CRAF activation mediated by HOP during MAPK signaling. Therefore, HOP is a regulator of CRAF kinase during activation of MAPK pathway and serves as a sensor of growth signaling beyond its client folding and maturation function.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Chaperone Complexes From The Endoplasmic Reticulum (ER) And The Cytosol Inhibit wt-p53 By Activation The ER To Cytosol Signaling. 94%
- Assembly and levels of P-TEFb depend on reversiblephosphorylation of cyclinT1 93%
- DYRK1A Interacts with the Tuberous Sclerosis Complex and Promotes mTORC1 Activity 93%
Similar papers in this journal
- Hsp90 and its co-chaperone Sti1 control TDP-43 misfolding and toxicity 94%
- Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma 91%
- CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor. 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.