Im Eunju, Yoon Jong Bok, Lee Han-Woong, Chung Kwang Chul
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
J Cell Physiol. 2017 Aug;232(8):2083-2093. doi: 10.1002/jcp.25607. Epub 2017 Feb 28.
Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, an RNA-dependent DNA polymerase that elongates telomeric DNA. hTERT displays several extra-telomeric functions that are independent of its telomere-regulatory function, including tumor progression, and neuronal cell death regulation. In this study, we evaluated these additional hTERT non-telomeric functions. We determined that hTERT interacts with several 19S and 20S proteasome subunits. The 19S regulatory particle and 20S core particle are part of 26S proteasome complex, which plays a central role in ubiquitin-dependent proteolysis. In addition, hTERT positively regulated 26S proteasome activity independent of its enzymatic activity. Moreover, hTERT enhanced subunit interactions, which may underlie hTERT's ability of hTERT to stimulate the 26S proteasome. Furthermore, hTERT displayed cytoprotective effect against ER stress via the activation of 26S proteasome in acute myeloid leukemia cells. Our data suggest that hTERT acts as a novel chaperone to promote 26S proteasome assembly and maintenance. J. Cell. Physiol. 232: 2083-2093, 2017. © 2016 Wiley Periodicals, Inc.
人端粒酶逆转录酶（hTERT）是端粒酶的催化亚基，端粒酶是一种依赖RNA的DNA聚合酶，可延长端粒DNA。hTERT具有多种与端粒调节功能无关的端粒外功能，包括肿瘤进展和神经元细胞死亡调节。在本研究中，我们评估了hTERT这些额外的端粒外功能。我们确定hTERT与几种19S和20S蛋白酶体亚基相互作用。19S调节颗粒和20S核心颗粒是26S蛋白酶体复合物的一部分，该复合物在泛素依赖性蛋白水解中起核心作用。此外，hTERT独立于其酶活性对26S蛋白酶体活性起到正向调节作用。而且，hTERT增强了亚基间的相互作用，这可能是hTERT刺激26S蛋白酶体能力的基础。此外，在急性髓系白血病细胞中，hTERT通过激活26S蛋白酶体对内质网应激发挥细胞保护作用。我们的数据表明，hTERT作为一种新型伴侣蛋白促进26S蛋白酶体的组装和维持。《细胞生理学杂志》232: 2083 - 2093, 2017。© 2016威利期刊公司
