SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor-suppressive function in the development of hepatocellular carcinoma

Carcinogenesis
Liang HuXin-Yuan Guan

Abstract

Pirh2 is a Ring-H2 domain containing E3 ubiquitin ligase that targets several important tumor suppressor genes for proteasomal degradation. Overexpression of Pirh2 is frequently detected in many clinical tumor tissues including hepatocellular carcinoma (HCC). However, the molecular mechanism of Pirh2 activation in tumorigenesis still remains poorly understood. In this study, we find a Pirh2-binding protein, SCYL1 binding protein 1 (SCYL1BP1), that can promote the ubiquitin-dependent degradation of Pirh2. SCYL1BP1 colocalized with Pirh2 in the cytoplasm and prevented its localization to the nucleus. Ectopic expression of SCYL1BP1 increased the expression of p53 and further inhibited the G(1)/S transition of HCC cell lines. Conversely, knock down of SCYL1BP1 restored the expression of Pirh2 and inhibited p53 at protein level. Functional assays found that reintroduction of SCYL1BP1 into HCC cell lines significantly inhibited cell proliferation, foci formation, colony formation in soft agar and tumor formation in nude mice, suggesting the strong tumor-suppressive function of SCYL1BP1 in HCC progression. Furthermore, SCYL1BP1 was found to be frequently downregulated in HCC clinical specimens compared to their paired non-tumor tissue...Continue Reading

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Citations

Mar 12, 2016·The Journal of Investigative Dermatology·Ying LiuJiang Chen
Sep 18, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Zhi-Ping YangWan-Xin Wu
Mar 26, 2015·Frontiers in Genetics·Kerstin BrinkmannHamid Kashkar
Oct 27, 2015·PloS One·Laure BridouxRené Rezsohazy
Feb 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ying LiuJiang Chen
Jan 10, 2021·Biochemical Pharmacology·Zhifei XuPeihua Luo

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