CDK5RAP3 is a co-factor for the oncogenic transcription factor STAT3.

CDK5RAP3 is a co-factor for the oncogenic transcription factor STAT3. Neoplasia. 2019 Nov 22;22(1):47-59 Authors: Egusquiaguirre SP, Liu S, Tošić I, Jiang K, Walker SR, Nicolais M, Saw TY, Xiang M, Bartel K, Nelson EA, Frank DA Abstract The transcription factor STAT3 regulates genes governing critical cellular processes such as proliferation, survival, and self-renewal. While STAT3 transcriptional function is activated rapidly and transiently in response to physiologic signals, through a variety of mechanisms it can become constitutively activated in the pathogenesis of cancer. This leads to chronic expression of genes that underlie malignant cellular behavior. However, STAT3 is known to interact with other proteins, which may modulate its function. Understanding these interactions can provide insights into novel aspects of STAT3 function and may also suggest strategies to therapeutically target the large number of cancers driven by constitutively activated STAT3. To identify critical modulators of STAT3 transcriptional function, we performed an RNA-interference based screen in a cell-based system that allows quantitative measurement of STAT3 activity. From this approach, we identified CDK5 kinase regulatory-subunit associated protein 3 (CDK5RAP3) as an enhancer of STAT3-dependent gene expression. We found that STAT3 transcriptional function is modulated by CDK5RAP3 in cancer cells, and silencing CDK5RAP3 reduces STAT3-mediated tum...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research