Tmub1 Suppresses Hepatocellular Carcinoma by Promoting the Ubiquitination of ΔNp63 Isoforms

Molecular Therapy Oncolytics
Hangwei FuPing Chen

Abstract

Transmembrane and ubiquitin-like domain-containing 1 (Tmub1) inhibits hepatocyte proliferation during liver regeneration, but its role in hepatocellular carcinoma (HCC) has yet to be revealed. In this study, we show that the levels of Tmub1 were significantly lower in HCC tissues and cells than they were in adjacent tissues and normal hepatic cells, and the low levels of Tmub1 indicated a poor prognosis in HCC patients. Xenograft growth assay revealed that Tmub1 represses HCC growth in vivo. In addition, Tmub1 formed a protein complex with apoptosis-associated protein tumor protein 63 (p63), especially with the ΔN isoforms (ΔNp63α, β, and γ). Further loss- and gain-of-function analyses indicated that Tmub1 promotes apoptosis of Hep3B and MHCC-LM3 cells. Tmub1 decreased the protein expression of ΔNp63, and the pro-apoptotic effect of Tmub1 can be reversed by ΔNp63 isoforms (α, β, and γ). Additionally, we report that Tmub1 promotes the ubiquitination and degradation of ΔNp63 proteins. Finally, we confirmed in HCC tissues that Tmub1 is negatively correlated with ΔNp63 and positively correlated with the level of apoptosis. Taken together, Tmub1 suppresses HCC by enhancing the ubiquitination and degradation of ΔNp63 isoforms to indu...Continue Reading

References

May 18, 2001·Biochemical and Biophysical Research Communications·M OsadaY Ikawa
Jun 28, 2002·Cancer Cell·Meera PatturajanDavid Sidransky
Aug 21, 2004·The Journal of Biological Chemistry·Michael J MaySankar Ghosh
Nov 16, 2004·Oncogene·Audrey PetitjeanClaude Caron de Fromentel
Jul 15, 2005·Journal of Cell Science·Maria Agnese Della FaziaGiuseppe Servillo
Jul 29, 2006·Journal of Gastroenterology and Hepatology·Fernando S RamalhoSérgio Zucoloto
Aug 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mario RossiGerry Melino
Aug 24, 2006·Neoplasia : an International Journal for Oncology Research·Ian R Watson, Meredith S Irwin
Feb 9, 2007·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Martina MüllerTobias Schilling
Apr 18, 2008·Cell Cycle·Stefania PieroniGiuseppe Servillo
Mar 4, 2009·Cellular & Molecular Immunology·Guo Yan LiuYi Zhi Yu
Mar 28, 2009·Nature·Mark Hochstrasser
Apr 21, 2010·Biochemical and Biophysical Research Communications·Heiko M MundtMartina Müller
Dec 9, 2016·International Journal of Molecular Sciences·Stephen R ArmstrongRoger P Leng
Feb 16, 2017·Advances in Experimental Medicine and Biology·Jeff L Staudinger
May 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Linshan HuZhi-Xiong Jim Xiao
May 27, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Paula ReventunMarta Saura

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Citations

Nov 19, 2020·Biomolecules·Zac SandyChristine K Schmidt
Feb 6, 2021·Bioscience Reports·Daniela BartoliMaria Agnese Della-Fazia
Aug 30, 2020·The FEBS Journal·Maria Agnese Della-FaziaGiuseppe Servillo

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Methods Mentioned

BETA
ubiquitination
xenograft
immunoprecipitation
coIP
coimmunoprecipitation
flow cytometry
PCR
transfection
pull-down
biopsy

Software Mentioned

Mascot
Prism
SPSS
ImageJ

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