Document Detail


Characterization of Cullin-box sequences that direct recruitment of Cul2-Rbx1 and Cul5-Rbx2 modules to Elongin BC-based ubiquitin ligases.
MedLine Citation:
PMID:  18187417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Elongin BC-box protein family includes the von Hippel-Lindau tumor suppressor and suppressor of cytokine signaling proteins, which are substrate recognition subunits of structurally related classes of E3 ubiquitin ligases composed of Elongin C-Elongin B-Cullin 2-Rbx1 (Cul2 ubiquitin ligases) or of Elongin C-Elongin B-Cullin 5-Rbx2 (Cul5 ubiquitin ligases). The Elongin BC complex acts as an adaptor that links a substrate recognition subunit to heterodimers of either Cullin 2 (Cul2) and RING finger protein Rbx1 or Cullin 5 (Cul5) and Rbx2. It has been shown ( Kamura, T., Maenaka, K., Kotoshiba, S., Matsumoto, M., Kohda, D., Conaway, R. C., Conaway, J. W., and Nakayama, K. I. (2004) Genes Dev. 18, 3055-3065 ) that interaction of BC-box proteins with their cognate Cul-Rbx module is determined by specific regions, called Cul2- or Cul5-boxes, located immediately downstream of their BC-boxes. Here, we investigate further the mechanisms governing assembly of BC-box proteins with their specific Cul-Rbx modules. Through purification and characterization of a larger collection of BC-box proteins that serve as substrate recognition subunits of Cul2 and Cul5 ubiquitin ligases and through structure-function studies, we define Cul2- and Cul5-boxes in greater detail. Although it previously appeared that there was little sequence similarity between Cul5- and Cul2-box motifs, analyses of newly identified BC-box proteins reveal that residues conserved in the Cul2-box represent a subset of those conserved in the Cul5-box. The sequence motif LPPhiP, which is conserved in most Cul5-boxes and has been suggested to specify assembly of Cul5 ligases, is compatible with Cul2 interaction. Finally, the spacing between BC- and Cullin-boxes is much more flexible than has been appreciated and can vary from as few as 3 and as many as approximately 80 amino acids. Taken together, our findings shed new light on the mechanisms by which BC-box proteins direct recruitment of Cullin-Rbx modules during reconstitution of ubiquitin ligases.
Authors:
Nawel Mahrour; William B Redwine; Laurence Florens; Selene K Swanson; Skylar Martin-Brown; William D Bradford; Karen Staehling-Hampton; Michael P Washburn; Ronald C Conaway; Joan W Conaway
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-01-10
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-05-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8005-13     Citation Subset:  IM    
Affiliation:
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs / genetics
Carrier Proteins / genetics*
Cell Line
Cullin Proteins / genetics*
DNA-Directed DNA Polymerase / genetics*
Humans
Multienzyme Complexes / genetics*
Protein Structure, Tertiary / genetics
Transcription Factors / genetics*
Ubiquitin-Protein Ligases / genetics*
Von Hippel-Lindau Tumor Suppressor Protein / genetics
Grant Support
ID/Acronym/Agency:
GM41628/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/CUL2 protein, human; 0/CUL5 protein, human; 0/Carrier Proteins; 0/Cullin Proteins; 0/Multienzyme Complexes; 0/RBX1 protein, human; 0/RNF7 protein, human; 0/Transcription Factors; 0/elongin; EC 2.7.7.-/DNA synthesome; EC 2.7.7.7/DNA-Directed DNA Polymerase; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/VHL protein, human; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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