KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases.
Potassium channel tetramerization domain (KCTD) proteins contain a bric-a-brac, tramtrak and broad complex (BTB) domain that is most similar to the tetramerization domain (T1) of voltage-gated potassium channels. Some BTB-domain-containing proteins have been shown recently to participate as substrate-specific adaptors in multimeric cullin E3 ligase reactions by recruiting proteins for ubiquitination and subsequent degradation by the proteasome. Twenty-two KCTD proteins have been found in the human genome, but their functions are largely unknown. In this study, we have characterized KCTD5, a new KCTD protein found in the cytosol of cultured cell lines. The expression of KCTD5 was upregulated post-transcriptionally in peripheral blood lymphocytes stimulated through the T-cell receptor. KCTD5 interacted specifically with cullin3, bound ubiquitinated proteins, and formed oligomers through its BTB domain. Analysis of the interaction with cullin3 showed that, in addition to the BTB domain, some amino acids in the N-terminus of KCTD5 are required for binding to cullin3. These findings suggest that KCTD5 is a substrate-specific adaptor for cullin3-based E3 ligases.
Bayón
Yolanda
Y
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Spain.
Trinidad
Antonio G
AG
de la Puerta
María L
ML
Del Carmen Rodríguez
María
M
Bogetz
Jori
J
Rojas
Ana
A
De Pereda
José M
JM
Rahmouni
Souad
S
Williams
Scott
S
Matsuzawa
Shu-Ichi
S
Reed
John C
JC
Crespo
Mariano Sánchez
MS
Mustelin
Tomas
T
Alonso
Andrés
A
D000595:Amino Acid Sequence; D002460:Cell Line; D002850:Chromatography, Gel; D044842:Cullin Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
C503645:CUL3 protein, human; D044842:Cullin Proteins; C521187:KCTD5 protein, human; D015221:Potassium Channels; D044767:Ubiquitin-Protein Ligases