Post-translational regulation of proto-oncogene ZBTB7A expression by p53 status in cancer cells: HSP90-dependent stabilization vs. p53-KLHL20-ubiquitin proteasomal degradation.

ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells. Interestingly, inhibition of HSP90 decreased ...
ZBTB7A expression in a variety of human cancer cells. ZBTB7A interacts with and is stabilized by HSP90. Inhibition of HSP90 by 17-AAG resulted in p53-dependent proteolysis of ZBTB7A via increased p53 expression and upregulation of the CUL3-dependent E3 ubiquitin ligase, KLHL20. Down-regulation of ZBTB7A resulted in the derepression of a major negative regulator of cell cycle progression, p21/CDKN1A. We discovered a new function of p53 regulating ZBTB7A expression through KLHL20-E3 ligase and proteasomal protein degradation system.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, Tumor, DNA-Binding Proteins, Humans, Neoplasms, Proto-Oncogenes, Transcription Factors, Tumor Suppressor Protein p53, Ubiquitin, Ubiquitin-Protein Ligases, Ubiquitination
Biochim Biophys Acta Gene Regul Mech
Date: Jun. 01, 2023
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