TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres
TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres
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DOI：
10.1101/gad.1077103
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发表时间：
2003-06-01
影响因子：
10.5
通讯作者：
Smith, S
中科院分区：
文献类型：
--
作者：
Chang, W;Dynek, JN;Smith, S
哺乳动物的端粒被序列特异的DNA结合蛋白TRF1所覆盖，TRF1是端粒长度的负调节因子。先前的研究结果表明，Tankyrase I通过ADP-核糖化作用将TRF1从端粒中释放出来，并促进端粒的延长。我们现在发现，端粒中TRF1的丢失会导致蛋白酶体泛素化和TRF1的降解，而这种降解是使TRF1远离端粒所必需的。TRF1的泛素化受其端粒结合状态的调节，只有端粒非结合形式的TRF1泛素化。我们的发现提示了一种新的机制，即TRF1(ADP-核糖化和泛素化)的顺序翻译后修饰来调节端粒酶对端粒的访问。
Mammalian telomeres are coated by the sequence-specific, DNA-binding protein, TRF1, a negative regulator of telomere length. Previous results showed that ADP-ribosylation of TRF1 by tankyrase I released TRF1 from telomeres and promoted telomere elongation. We now show that loss of TRF1 from telomeres results in ubiquitination and degradation of TRF1 by the proteasome and that degradation is required to keep TRF1 off telomeres. Ubiquitination of TRF1 is regulated by its telomere-binding status; only the telomere-unbound form of TRF1 is ubiquitinated. Our findings suggest a novel mechanism of sequential posttranslational modification of TRF1 (ADP-ribosylation and ubiquitination) for regulating access of telomerase to telomeres.