Investigation of the molecular mechanism of δ-catenin ubiquitination: Implication of β-TrCP-1 as a potential E3 ligase.
Ubiquitination, a post-translational modification, involves the covalent attachment of ubiquitin to the target protein. The ubiquitin-proteasome pathway and the endosome-lysosome pathway control the degradation of the majority of eukaryotic proteins. Our previous study illustrated that δ-catenin ubiquitination occurs in a glycogen synthase kinase-3 (GSK-3) phosphorylation-dependent manner. However, the molecular mechanism of δ-catenin ubiquitination is still unknown. Here, we show that the lysine residues required for ubiquitination are located mainly in the C-terminal portion of δ-catenin. In addition, we provide evidence that β-TrCP-1 interacts with δ-catenin and functions as an E3 ligase, mediating δ-catenin ubiquitin-proteasome degradation. Furthermore, we prove that both the ubiquitin-proteasome pathway and the lysosome degradation pathway are involved in δ-catenin degradation. Our novel findings on the mechanism of δ-catenin ubiquitination will add a new perspective to δ-catenin degradation and the effects of δ-catenin on E-cadherin involved in epithelial cell-cell adhesion, which is implicated in prostate cancer progression.
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Hridaya
H
Shrestha
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Tingting
T
Yuan
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Yongfeng
Y
He
Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Pyong-Gon
PG
Moon
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Nensi
N
Shrestha
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Taeyong
T
Ryu
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, 540-950, Republic of Korea.
So-Yeon
SY
Park
College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Young-Chang
YC
Cho
Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Chan-Hyeong
CH
Lee
Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Moon-Chang
MC
Baek
College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Sayeon
S
Cho
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Shishli
S
Simkhada
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, 540-950, Republic of Korea.
Hangun
H
Kim
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kwonseop
K
Kim
D000595:Amino Acid Sequence; D051177:Catenins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002853:Chromatography, Liquid; D015536:Down-Regulation; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D053719:Tandem Mass Spectrometry; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D025801:Ubiquitin; D044844:beta-Transducin Repeat-Containing Proteins; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D008239:Lysine; D000095002:Delta Catenin
Ubiquitination; β-TrCP-1; δ-Catenin