Hsp70–Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation
Abstract
This work dissects how cells monitor failure of proteasomes and trigger signaling responses defining whether cells survive proteotoxic stress or undergo apoptosis. The monitoring mechanism involves detection of a buildup of abnormal polypeptides released from ribosomes. Accordingly, the system simultaneously monitors effectiveness of several major processes, including protein synthesis, folding, and degradation. A special scaffold complex composed of heat shock protein 70 (Hsp70) and its cofactor Bcl-2–associated athanogene 3 (Bag3) links accumulation of abnormal polypeptide species with a number of protein kinases involved in various signal-transduction pathways. A startling finding is that an Hsp70–Bag3–regulated kinase, LATS1, regulates very early events of formation of protein aggregates; thus protein aggregation appears to be a tightly regulated process rather than the simple collapse of abnormal proteins.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 09, 2018
- Source ID
- 10.1073/pnas.1803130115
Entities
People
- Anatoli Meriin
- Arjun Narayanan
- Ibrahim I. Cissé
- Ilya Alexandrov
- Le Meng
- Michael Y. Sherman
- Xaralabos Varelas
Organizations
- Ariel University
- Boston University
- Congressionally Directed Medical Research Programs
- Massachusetts Institute of Technology
- National Cancer Institute
- National Heart, Lung, and Blood Institute