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Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2002 Aug 06; Vol. 99 (16), pp. 10353-8. Date of Electronic Publication: 2002 Jul 29. - Publication Year :
- 2002
-
Abstract
- The heterodimeric Elongin BC complex has been shown to interact in vitro and in cells with a conserved BC-box motif found in an increasing number of proteins including RNA polymerase II elongation factor Elongin A, suppressor of cytokine signaling (SOCS)-box proteins, and the von Hippel-Lindau tumor suppressor protein. Recently, the Elongin BC complex was found to function as an adaptor that links these BC-box proteins to a module composed of Cullin family members Cul2 or Cul5 and RING-H2 finger protein Rbx1 to reconstitute a family of E3 ubiquitin ligases that activate ubiquitylation by the E2 ubiquitin-conjugating enzyme Ubc5. As part of our effort to understand the functions of Elongin BC-based ubiquitin ligases, we exploited a modified yeast two-hybrid screen to identify a mammalian BC-box protein similar in sequence to Saccharomyces cerevisiae Mediator subunit Med8p. In this report we demonstrate (i) that mammalian MED8 is a subunit of the mammalian Mediator complex and (ii) that MED8 can assemble with Elongins B and C, Cul2, and Rbx1 to reconstitute a ubiquitin ligase. Taken together, our findings are consistent with the model that MED8 could function to recruit ubiquitin ligase activity directly to the RNA polymerase II transcriptional machinery.
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Cell Line
Cell Line, Transformed
DNA, Complementary
Dimerization
Elongin
Fungal Proteins metabolism
Humans
Ligases genetics
Liver metabolism
Mammals
Mediator Complex
Mice
Molecular Sequence Data
Nuclear Proteins metabolism
Rats
Spodoptera
Transcription Factors genetics
Tumor Suppressor Proteins metabolism
Von Hippel-Lindau Tumor Suppressor Protein
Cell Cycle Proteins metabolism
Cullin Proteins
Ligases metabolism
Saccharomyces cerevisiae Proteins
Transcription Factors metabolism
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligases
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 99
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 12149480
- Full Text :
- https://doi.org/10.1073/pnas.162424199