PDF(Pubmed)
Abstract：
STAM Binding Protein Like 1 (STAMBPL1), functions as a deubiquitinase (DUB) and plays a significant role in various types of cancers. However, its effect as a DUB participating in the HCC tumorigenesis and progression still unknown. In the study, the upregulation and strong prognosis value of STAMBPL1 were identified in HCC patients. Functionally, STAMBPL1 significantly promoted HCC cells proliferation and metastasis, and it interacts with TRAF2 and stabilize it via the deubiquitination at the K63 residue. The TRAF2 upregulation stabilized by STAMBPL1 overexpression transfers of P65 protein into the nucleus and activates the WNT/PI3K/ NF-kb signaling pathway. The 251-436 sites of STAMBPL1 particularly interact with the 294-496 sites of TRAF2, thereby exerting the function of DUB and removing the ubiquitin molecules attached to TRAF2. Our research unveiled a new function of STAMBPL1 in mediating TRAF2 deubiquitination and stabilization, thereby activating the WNT/PI3K/NF-kb signaling pathway, suggesting its potential as a novel biomarker and therapeutic target for HCC.
摘要：
STAM结合蛋白样1（STAMBPL1），作为去泛素酶（DUB），在各种类型的癌症中发挥重要作用。然而,其作为DUB参与HCC肿瘤发生和进展的作用尚不清楚。在研究中,在HCC患者中发现了STAMBPL1的上调和较强的预后价值.功能上,STAMBPL1显著促进肝癌细胞增殖和转移,它与TRAF2相互作用并通过K63残基的去泛素化使其稳定。STAMBPL1过表达稳定的TRAF2上调将P65蛋白转移到细胞核中并激活WNT/PI3K/NF-kb信号通路。STAMBPL1的251-436位点特别与TRAF2的294-496位点相互作用，从而发挥DUB的功能并去除与TRAF2连接的泛素分子。我们的研究揭示了STAMBPL1在介导TRAF2去泛素化和稳定中的新功能，从而激活WNT/PI3K/NF-kb信号通路，提示其作为肝癌新的生物标志物和治疗靶点的潜力。
