受體內(nèi)化是指受體蛋白通過(guò)質(zhì)膜凹陷從而脫離細(xì)胞膜進(jìn)入細(xì)胞質(zhì)的過(guò)程，內(nèi)化后受體失活,，信號(hào)轉(zhuǎn)導(dǎo)過(guò)程中斷。生長(zhǎng)激素受體(GHR)的內(nèi)化是一個(gè)高度調(diào)節(jié)的過(guò)程,，該過(guò)程依賴(lài)于多聚泛素連接酶Skp Cullin F-box (SCFβTrCP)的結(jié)合及其酶活性的大小,。近日，荷蘭烏德勒支大學(xué)Ger J. Strous等人發(fā)現(xiàn),，UBC13以及HSP70羧基末端相互作用蛋白(CHIP)對(duì)生長(zhǎng)激素受體內(nèi)吞是必須的,。相關(guān)研究發(fā)表在3月20的美國(guó)《生化周刊》（Journal of Biological Chemistry）上。
在SCFβTrCP介導(dǎo)的Lys48多聚泛素化過(guò)程中,，盡管β-轉(zhuǎn)導(dǎo)重復(fù)相容蛋白(βTrCP)和GHR可以發(fā)生特殊性相互作用,，而且該過(guò)程需求嚴(yán)格的泛素化活性，受體并不是泛素化過(guò)程中必須的目標(biāo)?，F(xiàn)在發(fā)現(xiàn),，GHR的內(nèi)化還需要Lys63連接的泛素鏈的形成,。鑒定發(fā)現(xiàn)，泛素結(jié)合酶Ubc13以及泛素連接酶HSP70羧基末端相互作用蛋白(CHIP)與這個(gè)過(guò)程有關(guān),，而且Ubc13的活化以及它與CHIP的相互作用先于GHR的內(nèi)化,。
除了βTrCP以外，CHIP可以特異性的與二聚化GHR在細(xì)胞質(zhì)基質(zhì)中的尾部相互作用,，表明Ubc13及CHIP都是調(diào)節(jié)細(xì)胞表面GHR的細(xì)胞因子,。這項(xiàng)研究有利于在治療癌癥及惡病質(zhì)中設(shè)計(jì)相關(guān)藥物來(lái)控制生長(zhǎng)激素信號(hào)。（生物谷Deepblue編譯）
doi: 10.1074/jbc.M111.302521
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Johan A. Slotman, Ana C. da Silva Almeida, Gerco C. Hassink, Robert H. A. van de Ven, Peter van Kerkhof, Hendrik J. Kuiken and Ger J. Strous.
Growth hormone receptor (GHR) endocytosis is a highly regulated process that depends on the binding and activity of the multimeric ubiquitin ligase, Skp Cullin F-box (SCFβTrCP). Despite a specific interaction between β-transducin repeat-containing protein (βTrCP) and the GHR, and a strict requirement for ubiquitination activity, the receptor is not an obligatory target for SCFβTrCP-directed Lys48 poly-ubiquitination.We now show that also Lys63-linked ubiquitin chain formation is required for GHR endocytosis. We identified both the ubiquitin conjugating enzyme Ubc13 and the ubiquitin ligase COOH-terminus of HSP70 interacting protein (CHIP) as being connected to this process. Ubc13 activity and its interaction with CHIP are preceding endocytosis of GHR.In addition to βTrCP, CHIP interacts specifically with the cytosolic tails of the dimeric GHR, identifying both Ubc13 and CHIP as novel factors in the regulation of cell surface availability of GHR.
