CSN5/JAB1 interacts with the centromeric components CENP-T and CENP-W and regulates their proteasome-mediated degradation.
The CENP-T·CENP-W complex is a recently identified inner centromere component that plays crucial roles in the formation of a functional kinetochore involved in cell division during mitosis. Using yeast two-hybrid screening, we identified an interaction between CENP-T and CSN5, the fifth component of the COP9 signalosome and a key modulator of the cell cycle and cancer. Co-immunoprecipitation revealed that CSN5 directly interacts with both CENP-T and CENP-W. Ectopically expressed CSN5 promoted the ubiquitin- and proteasome-dependent degradation of CENP-T·CENP-W. The formation of a CENP-T·CENP-W complex greatly enhanced the stabilities of the respective proteins, possibly by blocking CSN5-mediated degradation. Furthermore, dysregulation of CSN5 induced severe defects in the recruitment of CENP-T·CENP-W to the kinetochore during the prophase stage of mitosis. Thus, our results indicate that CSN5 regulates the stability of the inner kinetochore components CENP-T and CENP-W, providing the first direct link between CSN5 and the mitotic apparatus, highlighting the role of CSN5 as a multifunctional cell cycle regulator.
Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
Younghwa
Y
Chun
Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
Miae
M
Lee
Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
Byoungwoo
B
Park
Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea. Electronic address: leesoojin@cnu.ac.kr.
Soojin
S
Lee
D000075686:COP9 Signalosome Complex; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011418:Prophase / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
C534001:CENPT protein, human; C534000:CENPW protein, human; D002868:Chromosomal Proteins, Non-Histone; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D025801:Ubiquitin; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D046988:Proteasome Endopeptidase Complex
CENP-W, COP9 Signalsome; CSN5; Cancer; Centromeres; Kinetochore, Proteasome, Protein Degradation, CENP-T