Casitas B-cell lymphoma (Cbl) proteins protect mammary epithelial cells from proteotoxicity of active c-Src accumulation
Abstract
Casitas B-cell lymphoma (Cbl) family proteins are RING finger-containing E3 ubiquitin ligases involved in degradation of activated tyrosine kinases. Previous studies in Cbl-deficient models focused primarily on the consequences of persistent tyrosine kinase signaling resulting in uncontrolled cell activation and proliferation. In the present study, we provide evidence that, in the complete absence of Cbl family proteins, failure to turn over active tyrosine kinases induces irreparable breakdown of the homeostasis of the protein milieu in primary mouse mammary epithelial cells and triggers stress-mediated cell death. Thus, our data reveal that well-regulated removal of active tyrosine kinases is essential for cell survival, an aspect of Cbl family protein functions that has not been previously fully appreciated.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 05, 2016
- Source ID
- 10.1073/pnas.1615677113
Entities
People
- Aleata Triplett
- Carol Heckman
- Chandrani Mukhopadhyay
- Kay-uwe Wagner
- Mayumi Naramura
- Tom Bargar
Organizations
- Bowling Green State University
- Congressionally Directed Medical Research Programs
- National Institute of General Medical Sciences
- University of Nebraska Medical Center
- University of Nebraska–Lincoln