A molecular basis for stabilization of the von hippel-lindau (VHL) tumor suppressor protein by components of the VHL ubiquitin ligase

Simple item page
dc.contributor.authorKamura, Takumi
dc.contributor.authorBrower, Christopher S.
dc.contributor.authorConaway, Ronald C.
dc.contributor.authorConaway, Joan Weliky
dc.creator.orcidhttps://orcid.org/0000-0003-0289-5541
dc.date.accessioned2023-01-27T18:15:56Z
dc.date.available2023-01-27T18:15:56Z
dc.date.issued2002
dc.description.abstractThe multiprotein von Hippel-Lindau (VHL) tumor suppressor (CBCVHL, Cul2-ElonginBC-VHL) and SCF (Skp1-Cul1/Cdc53-F-box protein) complexes are members of structurally related families of E3 ubiquitin ligases that use a heterodimeric module composed of a member of the Cullin protein family and the RING finger protein Rbx1 (ROC1/Hrt1) to activate ubiquitylation of target proteins by the E2 ubiquitin-conjugating enzymes Ubc5 and Cdc34. VHL and F-box proteins function as the substrate recruitment subunits of CBCVHLand SCF complexes, respectively. In cells, many F-box proteins are short lived and are proposed to be ubiquitylated by an autocatalytic mechanism and destroyed by the proteasome following assembly into SCF complexes. In contrast, the VHL protein is stabilized by interaction with the Elongin B and C subunits of CBCVHL in cells. In this report, we have presented direct biochemical evidence that unlike the F-box protein Cdc4, which is ubiquitylated in vitro by Cdc34 in the context of the SCF, the VHL protein is protected from Ubc5-catalyzed ubiquitylation following assembly into the CBCVHL complex. CBCVHL is continuously required for negative regulation of hypoxia-inducible transcription factors in normoxic cells and of SCF complexes, many of which function only transiently during the cell cycle or in response to cellular signals. Our findings provide a molecular basis for the different modes of cellular regulation of VHL and F-box proteins and are consistent with the known roles of CBCVHL.en_US
dc.identifier.citationThis is the published version of an article that is available at https://doi.org/10.1074/jbc.m203344200. Recommended citation: Kamura, T., Brower, C. S., Conaway, R. C., & Conaway, J. W. (2002). A molecular basis for stabilization of the von hippel-lindau (VHL) tumor suppressor protein by components of the VHL ubiquitin ligase. Journal of Biological Chemistry, 277(33), 30388–30393. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.identifier.urihttps://hdl.handle.net/11274/14347
dc.identifier.urihttps://doi.org/10.1074/jbc.m203344200
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.rights.licenseCC-BY 4.0
dc.subjectHigh pressure liquid chromatographyen_US
dc.subjectCul2-Elongin BCen_US
dc.subjectGlutathione S-transferaseen_US
dc.titleA molecular basis for stabilization of the von hippel-lindau (VHL) tumor suppressor protein by components of the VHL ubiquitin ligaseen_US
dc.typeArticleen_US

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
Brower-A Molecular Basis for Stabilization of the von Hippel-Lindau.pdf
Size:
295.94 KB
Format:
Adobe Portable Document Format
Description:
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.68 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Biology