Affiliation:
1. Department of Physiology, School of Life Sciences Chongqing University Chongqing China
2. Molecular Physiology Division Zoology Department Faculty of Science Beni‐Suef University Beni‐Suef Egypt
3. Department of Oncology Faculty of Medicine Linköping University Sweden
4. Department of Biomedical and Clinical Sciences Faculty of Medicine Linköping University Sweden
5. Department of Pathology Chongqing Hygeia Hospital Chongqing China
Abstract
AbstractBackgroundThe MYC oncoprotein, also known as the master regulator of genes, is a transcription factor that regulates numerous physiological processes, including cell cycle control, apoptosis, protein synthesis and cell adhesion, among others. MYC is overexpressed in approximately 70% of human cancers. Given its pervasive role in cancer biology, MYC down‐regulation has become an attractive cancer treatment strategy.MethodsThe CRISPR/Cas9 method was used to produce KO cell models. Western blot was used to analyzed the expressions of MYC and TATA‐binding proteinassociated factors 10 (TAF10) in cancer cells (MCF7, A549, HepG2 cells) Cell culture studies were performed to determine the mechanisms by which small molecules (Z363119456, Z363) affects MYC and TAF10 expressions and functions. Mouse studies were carried out to investigate the impact of Z363 regulation on tumor growth.ResultsZ363 activate Thyroid hormone Receptor‐interacting Protein 12 (TRIP12), which phosphorylates MYC at Thr58, resulting in MYC ubiquitination and degradation and thereby regulating MYC target genes. Importantly, TRIP12 also induces TAF10 degradation, which reduces MYC protein levels. TRIP12, an E3 ligase, controls MYC levels both directly and indirectly by inhibiting MYC or TAF10 activity.ConclusionsIn summary,these results demonstrate the anti‐cancer properties of Z363, a small molecule that is co‐regulated by TAF10 and MYC.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
Molecular Medicine,Medicine (miscellaneous)
Cited by
4 articles.
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