Abbreviated Journal Title
telomere; hTERT; Hsp90; ubiquitin; proteolysis; CELLULAR INHIBITOR; PROTEINS; HSP90; RECEPTOR; CANCER; RING; TIME; P23; Cell Biology; Developmental Biology; Genetics & Heredity
Telomere homeostasis is regulated by telomerase and a collection of associatedproteins. Telomerase is, in turn, regulated by post-translational modifications of the rate-limiting catalytic subunit hTERT. Here we show that disruption of Hsp90 by geldanamycin promotes efficient ubiquitination and proteasome-mediated degradation of hTERT. Furthermore, we have used the yeast two-hybrid method to identify a novel RING finger gene (MKRN1) encoding an E3 ligase that mediates ubiquitination of hTERT. Overexpression of MKRN1 in telomerase-positive cells promotes the degradation of hTERT and decreases telomerase activity and subsequently telomere length. Our data suggest that MKRN1 plays an important role in modulating telomere length homeostasis through a dynamic balance involving hTERT protein stability.
Genes & Development
Kim, Jun Hyun; Park, Sun-Mi; Kang, Mi Ran; Oh, Sue-Young; Lee, Tae H.; Muller, Mark T.; and Chung, In Kwon, "Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT" (2005). Faculty Bibliography 2000s. 5349.