Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT.
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Kim JH, Park SM, Kang MR, Oh SY, Lee TH, Muller MT, Chung IK
Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT.
Genes Dev. 2005 Apr 1;19(7):776-81.
- PubMed ID
- 15805468 [ View in PubMed]
- Abstract
Telomere homeostasis is regulated by telomerase and a collection of associated proteins. 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.