A Sleeping Beauty transposon-mediated forward genetic screen in mice identified Cnot1 as a candidate colorectal cancer gene (CRC). CNOT1 is a central subunit of the CCR4-NOT (CNOT) deadenylase complex that regulates mRNA expression through multiple mechanisms, such as deadenylation. Our study suggests a model that CNOT1 protects cells from severe endoplasmic reticulum (ER) stress induced apoptosis through limiting the levels of TXNIP via promoting deadenylation and degradation of TXNIP mRNA transcripts. We also fund that CNOT1 plays a role in limiting cellular ER stress. Given that TXNIP is activated to promote apoptosis in response to extreme cellular stresses, such as ER stress, and that cancer cells commonly experience high levels of ER stress, increased activity of CNOT1 may be a mechanism that allows cancer cells to survive by protecting against cell stress-induced apoptosis.
University of Minnesota Ph.D. dissertation. December 2013. Major: Biochemistry, Molecular Bio, and Biophysics. Advisors: Robert Cormier, Ph.D. and and Patricia Scott, Ph.D. 1 computer file (PDF); xii, 236 pages.
Functional characterization of the candidate colorectal cancer gene CNOT1.
Retrieved from the University of Minnesota Digital Conservancy,
Content distributed via the University of Minnesota's Digital Conservancy may be subject to additional license and use restrictions applied by the depositor.