Dmitriev Ruslan I, Okkelman Irina A, Abdulin Roman A, Shakhparonov Mikhail I, Pestov Nikolay B
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
Cell Tissue Res. 2009 Jun;336(3):521-7. doi: 10.1007/s00441-009-0785-y. Epub 2009 Apr 24.
TTC4 (tetratricopeptide repeat domain protein 4) is a putative tumor suppressor involved in the transformation of melanocytes. At present, the relationships between TTC4 and DNA replication proteins are largely unknown, as are the tissue distribution and subcellular localization of TTC4. Using reverse transcription with the polymerase chain reaction, we have observed that the murine TTC4 gene is ubiquitously expressed. Analysis of the TTC4 subcellular localization has shown that, upon overexpression, TTC4 localizes to the cytoplasm. Interestingly, co-expression with a known protein interaction partner, hampin/MSL1, results in the nuclear translocation of the TTC4 protein. The subcellular localization of endogenous TTC4 depends, however, on the cell cycle: it is mostly nuclear in the G1 and S phases and is evenly distributed between the nucleus and cytoplasm in G2. The nuclear transport of TTC4 is apparently a complex process dependent on interactions with other proteins during the progression of the cell cycle. Thus, the dynamic character of the nuclear accumulation of TTC4 might be a potential link with regard to its function in tumor suppression.
TTC4（四肽重复结构域蛋白4）是一种推定的肿瘤抑制因子，参与黑素细胞的转化。目前，TTC4与DNA复制蛋白之间的关系很大程度上尚不清楚，TTC4的组织分布和亚细胞定位也是如此。通过聚合酶链反应进行逆转录，我们观察到小鼠TTC4基因广泛表达。对TTC4亚细胞定位的分析表明，过表达时，TTC4定位于细胞质。有趣的是，与已知的蛋白质相互作用伴侣hampin/MSL1共表达会导致TTC4蛋白发生核转位。然而，内源性TTC4的亚细胞定位取决于细胞周期：在G1期和S期它大多位于细胞核中，在G2期则在细胞核和细胞质之间均匀分布。TTC4的核转运显然是一个复杂的过程，在细胞周期进程中依赖于与其他蛋白质的相互作用。因此，TTC4核积累的动态特性可能是其在肿瘤抑制功能方面的一个潜在联系。
