Endocrine Oncology Research, Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.
FEBS Lett. 2011 Aug 4;585(15):2537-44. doi: 10.1016/j.febslet.2011.07.005. Epub 2011 Jul 13.
Human cancers utilise telomerase to maintain telomeres and prohibit cell senescence. Human telomerase reverse transcriptase (hTERT), an essential component of this complex, is regulated at the level of gene transcription. Using SILAC-proteomic analysis and molecular studies, we identified the AAA+ ATPase, RuvBl2 as a transcriptional regulator of hTERT and established that this regulation is through cooperation with Ets-2. In colon cancer patients, nuclear expression of RuvBl2 associated with nuclear expression of hTERT, pEts2 and advanced nodal disease (P<0.01, P=0.05 and P=0.03 respectively, n=170). These data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer which has functional and clinical consequences.
人类癌症利用端粒酶来维持端粒并防止细胞衰老。人类端粒酶逆转录酶（hTERT）是该复合物的一个重要组成部分，其转录水平受到调控。通过 SILAC 蛋白质组学分析和分子研究，我们鉴定出 AAA+ATP 酶 RuvBl2 是 hTERT 的转录调节剂，并确定这种调节是通过与 Ets-2 合作实现的。在结肠癌患者中，RuvBl2 的核表达与 hTERT、pEts2 和高级淋巴结病的核表达相关（P<0.01、P=0.05 和 P=0.03，n=170）。这些数据确凿地表明，RuvBl2 在结肠癌中通过 Ets-2 介导的 hTERT 调节中发挥作用，具有功能和临床意义。
