受体内化是指受体蛋白通过质膜凹陷从而脱离细胞膜进入细胞质的过程，内化后受体失活，信号转导过程中断。生长激素受体(GHR)的内化是一个高度调节的过程，该过程依赖于多聚泛素连接酶Skp Cullin F-box (SCFβTrCP)的结合及其酶活性的大小。近日，荷兰乌德勒支大学Ger J. Strous等人发现，UBC13以及HSP70羧基末端相互作用蛋白(CHIP)对生长激素受体内吞是必须的。相关研究发表在3月20的美国《生化周刊》（Journal of Biological Chemistry）上。
在SCFβTrCP介导的Lys48多聚泛素化过程中，尽管β-转导重复相容蛋白(βTrCP)和GHR可以发生特殊性相互作用，而且该过程需求严格的泛素化活性，受体并不是泛素化过程中必须的目标。现在发现，GHR的内化还需要Lys63连接的泛素链的形成。鉴定发现，泛素结合酶Ubc13以及泛素连接酶HSP70羧基末端相互作用蛋白(CHIP)与这个过程有关，而且Ubc13的活化以及它与CHIP的相互作用先于GHR的内化。
除了βTrCP以外，CHIP可以特异性的与二聚化GHR在细胞质基质中的尾部相互作用，表明Ubc13及CHIP都是调节细胞表面GHR的细胞因子。这项研究有利于在治疗癌症及恶病质中设计相关药物来控制生长激素信号。（生物谷Deepblue编译）
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.
