Dataset Information


Ubiquitination of lysine-331 by Kaposi's sarcoma-associated herpesvirus protein K5 targets HFE for lysosomal degradation.

ABSTRACT: The nonclassical MHC class I-related (MHC-I) molecule HFE controls cellular iron homeostasis by a mechanism that has not been fully elucidated. We examined the regulation of HFE by K5, the E3 ubiquitin ligase encoded by Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), that is known to down-regulate classical MHC-I. K5 down-regulated HFE efficiently, using polyubiquitination of the membrane proximal lysine in the HFE cytoplasmic tail (K331), to target the molecule for degradation via ESCRT1/TSG101-dependent sorting from endosomes to multivesicular bodies (MVBs)/lysosomes. In the primary effusion lymphoma cell line BC-3, which carries latent KSHV, HFE was degraded rapidly upon virus reactivation. HFE was ubiquitinated on lysine-331 in unactivated BC-3 cells, conditions where K5 was not detectable, consistent with an endogenous E3 ubiquitin ligase controlling HFE expression. The results show regulated expression of HFE by ubiquitination, consistent with a role in cellular iron homeostasis, a molecular mechanism targeted by KSHV to achieve a positive iron balance.


PROVIDER: S-EPMC2941293 | BioStudies | 2010-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2008-01-01 | S-EPMC2234200 | BioStudies
2010-01-01 | S-EPMC3551259 | BioStudies
2010-01-01 | S-EPMC2855335 | BioStudies
2014-01-01 | S-EPMC4136276 | BioStudies
2011-01-01 | S-EPMC3072377 | BioStudies
2012-01-01 | S-EPMC3446615 | BioStudies
2003-01-01 | S-EPMC140772 | BioStudies
2013-01-01 | S-EPMC3836740 | BioStudies
1000-01-01 | S-EPMC1440841 | BioStudies
2015-01-01 | S-EPMC6660136 | BioStudies