Unknown

Dataset Information

0

The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1.


ABSTRACT: Inactivation of the von Hippel-Lindau (VHL) tumor suppressor is associated with renal carcinoma, hemangioblastoma and pheochromocytoma. The VHL protein is a component of a ubiquitin ligase complex that ubiquitinates and degrades hypoxia inducible factor-? (HIF-?). Degradation of HIF-? by VHL is proposed to suppress tumorigenesis and tumor angiogenesis. Several lines of evidence also suggest important roles for HIF-independent VHL functions in tumor suppression and other biological processes. Using GST-VHL pull-down experiment and mass spectrometry, we detected an interaction between VHL and heterochromatin protein 1 (HP1). We identified a conserved HP1-binding motif (PXVXL) in the ? domain of VHL, which is disrupted in a renal carcinoma-associated P81S mutant. We show that the VHL P81S mutant displays reduced binding to HP1, yet retains the ability to interact with elongin B, elongin C, and cullin 2 and is fully capable of degrading HIF-?. We also demonstrate that HP1 increases the chromatin association of VHL. These results suggest a role for the VHL-HP1 interaction in VHL chromatin targeting.

SUBMITTER: Lai Y 

PROVIDER: S-EPMC3274591 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1.

Lai Yanlai Y   Song Meihua M   Hakala Kevin K   Weintraub Susan T ST   Shiio Yuzuru Y  

Archives of biochemistry and biophysics 20120103 2


Inactivation of the von Hippel-Lindau (VHL) tumor suppressor is associated with renal carcinoma, hemangioblastoma and pheochromocytoma. The VHL protein is a component of a ubiquitin ligase complex that ubiquitinates and degrades hypoxia inducible factor-α (HIF-α). Degradation of HIF-α by VHL is proposed to suppress tumorigenesis and tumor angiogenesis. Several lines of evidence also suggest important roles for HIF-independent VHL functions in tumor suppression and other biological processes. Usi  ...[more]

Similar Datasets

| S-EPMC1479743 | biostudies-literature
| S-EPMC4515828 | biostudies-literature
| S-EPMC2064591 | biostudies-literature
| S-EPMC1180379 | biostudies-literature
| S-EPMC9812266 | biostudies-literature
| S-EPMC2995849 | biostudies-literature
| S-EPMC3113667 | biostudies-literature
| S-EPMC3014987 | biostudies-literature
| S-EPMC4238297 | biostudies-literature
| S-EPMC2175351 | biostudies-literature