Zhang Fan, Laiho Marikki
Haartman Institute and Molecular and Cancer Biology Program, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, P.O. Box 63, FIN-00014 Helsinki, Finland.
Exp Cell Res. 2003 Dec 10;291(2):275-81. doi: 10.1016/j.yexcr.2003.07.007.
Transforming growth factor-beta (TGF-beta) signaling mainly relies on the TGF-beta receptor-Smad pathway. Meanwhile, TGF-beta binding to its receptors initiates the degradation of several key components of its signaling pathway. The degradation of these components, including both positive and negative transducers, is mediated by the ubiquitin-proteasome system. Inhibition of the proteasome activity causes accumulation of these components in the cells and modulates TGF-beta signaling in a time-dependent and gene-specific manner. The accelerated degradation of TGF-beta signaling components via the proteasome system has been found in a number of tumors, indicating that dysregulated proteasomal degradation is a novel pathway how tumor cells silence TGF-beta signaling.
转化生长因子-β（TGF-β）信号传导主要依赖于TGF-β受体-Smad途径。同时，TGF-β与其受体结合会引发其信号通路中几个关键成分的降解。这些成分的降解，包括正向和负向转导子，均由泛素-蛋白酶体系统介导。蛋白酶体活性的抑制会导致这些成分在细胞中积累，并以时间依赖性和基因特异性方式调节TGF-β信号传导。通过蛋白酶体系统加速TGF-β信号成分的降解已在许多肿瘤中被发现，这表明蛋白酶体降解失调是肿瘤细胞使TGF-β信号沉默的一种新途径。
