Robarts Research Institute, Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, Ontario, Canada N6A 5B7.
Robarts Research Institute, Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street North, London, Ontario, Canada N6A 5B7
Open Biol. 2017 Jun;7(6). doi: 10.1098/rsob.170081.
RanBPM (Ran-binding protein M, also called RanBP9) is an evolutionarily conserved, ubiquitous protein which localizes to both nucleus and cytoplasm. RanBPM has been implicated in the regulation of a number of signalling pathways to regulate several cellular processes such as apoptosis, cell adhesion, migration as well as transcription, and plays a critical role during development. In addition, RanBPM has been shown to regulate pathways implicated in cancer and Alzheimer's disease, implying that RanBPM has important functions in both normal and pathological development. While its functions in these processes are still poorly understood, RanBPM has been identified as a component of a large complex, termed the CTLH (C-terminal to LisH) complex. The yeast homologue of this complex functions as an E3 ubiquitin ligase that targets enzymes of the gluconeogenesis pathway. While the CTLH complex E3 ubiquitin ligase activity and substrates still remain to be characterized, the high level of conservation between the complexes in yeast and mammals infers that the CTLH complex could also serve to promote the degradation of specific substrates through ubiquitination, therefore suggesting the possibility that RanBPM's various functions may be mediated through the activity of the CTLH complex.
RanBPM（Ran 结合蛋白 M，也称为 RanBP9）是一种进化上保守的、普遍存在的蛋白质，定位于细胞核和细胞质。RanBPM 已被牵连到多种信号通路的调节中，以调节细胞凋亡、细胞黏附、迁移以及转录等多种细胞过程，并在发育过程中发挥关键作用。此外，RanBPM 已被证明可调节与癌症和阿尔茨海默病相关的通路，这意味着 RanBPM 在正常和病理发育中都具有重要功能。虽然其在这些过程中的功能仍知之甚少，但 RanBPM 已被确定为一个称为 CTLH（LisH 端到 C 端）复合物的大型复合物的组成部分。该复合物的酵母同源物作为一种 E3 泛素连接酶，靶向糖异生途径的酶。虽然 CTLH 复合物的 E3 泛素连接酶活性和底物仍有待表征，但复合物在酵母和哺乳动物之间的高度保守性推断，CTLH 复合物也可能通过泛素化促进特定底物的降解，因此表明 RanBPM 的各种功能可能通过 CTLH 复合物的活性来介导。
