SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor suppressive function in the development of hepatocellular carcinoma
Menée in vitro, in vivo et à partir d'échantillons tumoraux prélevés sur des patients atteints d'un carcinome hépatocellulaire, cette étude suggère que la protéine SCYL1BP1 joue un rôle de suppresseur de tumeurs
Pirh2 is a Ring-H2 domain containing E3 ubiquitin ligase which target 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 the present study, we find a Pirh2 binding protein SCYL1 binding protein 1 (SCYL1BP1) can promote the ubiquitin-dependent degradation of Pirh2. SCYL1BP1 co-localized with Pirh2 in the cytoplasm and prevented its localization to the nucleus. Ectopic expression of SCYL1BP1 increased the expression of p53 and further in hibited the G1/S transition of HCC cell lines. Conversely, knock down of SCYL1BP1 restored the expression 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 down-regulated in HCC clinical specimens compared to their paired non-tumor tissues by immunohistochemical (IHC) staining. Taken together, our data suggested that the interaction of SCYL1BP1/Pirh2 could accelerate Pirh2 degradation through an ubiquitin-dependent pathway. SCYL1BP1 may function as an important tumor suppressor gene in HCC development.
http://carcin.oxfordjournals.org/content/early/2012/05/07/carcin.bgs162.abstract