Title

Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT

Authors

Authors

J. H. Kim; S. M. Park; M. R. Kang; S. Y. Oh; T. H. Lee; M. T. Muller;I. K. Chung

Comments

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Abbreviated Journal Title

Genes Dev.

Keywords

telomere; hTERT; Hsp90; ubiquitin; proteolysis; CELLULAR INHIBITOR; PROTEINS; HSP90; RECEPTOR; CANCER; RING; TIME; P23; Cell Biology; Developmental Biology; Genetics & Heredity

Abstract

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.

Journal Title

Genes & Development

Volume

19

Issue/Number

7

Publication Date

1-1-2005

Document Type

Article

Language

English

First Page

776

Last Page

781

WOS Identifier

WOS:000228154100002

ISSN

0890-9369

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