PTOP interacts with POT1 and regulates its localization to telomeres
PTOP interacts with POT1 and regulates its localization to telomeres
复制标题
DOI：
10.1038/ncb1142
复制
发表时间：
2004-07-01
影响因子：
21.3
通讯作者：
Zhou, SY
中科院分区：
文献类型：
--
作者：
Liu, D;Safari, A;Zhou, SY
端粒维持与癌症和衰老有关，需要多种端粒因子之间的合作，包括端粒酶、TRF 1、TRF 2、RAP 1、TIN 2、端锚聚合酶、PINX 1和POT 1（参考文献1-12）。POT 1属于一个包含寡核苷酸结合（OB）折叠的蛋白质家族，包括Oxytricha nova TEBP、Cdc 13和spPot 1，其特异性识别端粒单链DNA（ssDNA）（10，13 -19）。在人类细胞中，POT 1对端粒ssDNA的加载控制端粒酶介导的端粒延长（12）。令人惊讶的是，缺乏OB折叠的人POT 1突变体仍然被招募到端粒。然而，这种招募发生的确切机制仍不清楚。在这里，我们确定了一种新的端粒蛋白，PTOP，它与POT 1和TIN 2相互作用。PTOP与POT 1的羧基末端结合并将其募集到端粒。通过RNA干扰（RNAi）抑制PTOP或破坏PTOP-POT 1相互作用阻碍了POT 1在端粒上的定位。此外，PTOP和POT 1上各自的相互作用结构域的表达单独延长了人细胞中的端粒长度。因此，PTOP与POT 1异源二聚化并调节POT 1端粒募集和端粒长度。
Telomere maintenance has been implicated in cancer and ageing, and requires cooperation between a multitude of telomeric factors, including telomerase, TRF1, TRF2, RAP1, TIN2, Tankyrase, PINX1 and POT1 (refs 1-12). POT1 belongs to a family of oligonucleotide-binding (OB)-fold-containing proteins that include Oxytricha nova TEBP, Cdc13, and spPot1, which specifically recognize telomeric single-stranded DNA (ssDNA)(10,13-19). In human cells, the loading of POT1 to telomeric ssDNA controls telomerase-mediated telomere elongation(12). Surprisingly, a human POT1 mutant lacking an OB fold is still recruited to telomeres. However, the exact mechanism by which this recruitment occurs remains unclear. Here we identify a novel telomere protein, PTOP, which interacts with both POT1 and TIN2. PTOP binds to the carboxyl terminus of POT1 and recruits it to telomeres. Inhibition of PTOP by RNA interference (RNAi) or disruption of the PTOP-POT1 interaction hindered the localization of POT1 to telomeres. Furthermore, expression of the respective interaction domains on PTOP and POT1 alone extended telomere length in human cells. Therefore, PTOP heterodimerizes with POT1 and regulates POT1 telomeric recruitment and telomere length.