Description:
<jats:p>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 (<jats:italic>MKRN1</jats:italic>) encoding an E3 ligase that mediates ubiquitination of hTERT. Overexpression of<jats:italic>MKRN1</jats:italic>in telomerase-positive cells promotes the degradation of hTERT and decreases telomerase activity and subsequently telomere length. Our data suggest that<jats:italic>MKRN1</jats:italic>plays an important role in modulating telomere length homeostasis through a dynamic balance involving hTERT protein stability.</jats:p>