HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle

• DOI: 10.7150/ijbs.72014
• Publication Date: 2022-05-04T02:00:35Z
• Authors: Zhiyuan Zhang; Qi Wu; Meimiao Fang; Yu Liu; Ji Jiang; Qingyang Feng; Ronggui Hu; Jianmin Xu
• Keywords: Ribosomal Proteins; 0301 basic medicine; 03 medical and health sciences; Ubiquitin-Protein Ligases; Cell Cycle; Ubiquitination; Humans; Colorectal Neoplasms; Cell Division; Research Paper; Cell Proliferation

Aims: Colorectal cancer (CRC) has high mortality and morbidity rates; however, the mechanism of CRC cells uncontrolled proliferation is unclarified, E3 ligases are widely reported to have crucial functions in cancers.HERC3 was once recognized as an important role CRC, however its effects on cell cycle blank.Methods: Correlation between HERC3 clinical characteristics analyzed.Coimmunoprecipitation, mass spectrometry analysis GST-pull down were performed identify interacting-proteins HERC3.Expression pattern RPL23A correlation researched via qRT-PCR, western blot immunohistochemistry.In vivo vitro gain-and loss-of-function assays rescue experiments concentrating HERC3-RPL23A axis terms conducted.The ubiquitination regulatory identified ubiquitylation assays, cycloheximide analysis.GSEA aided research potential functional validated by assays.Results: expression decreased gradually from colorectal tissues healthy individuals adjacent-tumors normal tissue patients, tumor could inhibit arrest G0-G1 phase.RPL23A which one target be overexpressed serve a prognostic biomarker CRC.RPL23A also independently regulate attenuate influence CRC.In addition, directly interacted with served ligase degrade K48-dependant manner through HECT domain.Furthermore, p21 further modulate protein c-Myc regulating RPL23A.Conclusion: controlled proliferation, regulated c-Myc/p21 targeting for degradation.