Cdh1 controls the stability of TACC3.
Transforming acidic coiled-coil protein 3 (TACC3) was reported to be important for regulating mitotic spindle assembly and chromosome segregation. While the protein level of TACC3 was shown to be altered during cell cycle progression, the molecular mechanism in controlling TACC3 level is unclear. Here, we show that TACC3 protein level can be regulated by Cdh1, a well known activator of anaphase-promoting complex/cyclosome. We identified Cdh1 as an interacting partner of TACC3 by a yeast array screen. Both in vitro and in vivo binding studies indicated that TACC3 can form complexes with Cdh1. Depletion of endogenous Cdh1 prolonged TACC3 protein level during mitotic exit. Alteration of Cdh1 level by ectopic overexpression or siRNA knockdown correlated well with an increase or decrease of ubiquitinated TACC3, respectively. Furthermore, the domain mapping studies of TACC3 revealed that multiple domains are involved in Cdh1-regulated degradation of TACC3. Altogether, our findings suggest that Cdh1 controls TACC3 protein stability during mitotic exit.
Jeng
Jen-Chong
JC
Graduate Institute of Life Sciences, National Defense Medical Center and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Lin
Ying-Mei
YM
Lin
Chiou-Hong
CH
Shih
Hsiu-Ming
HM
D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D055550:Protein Stability; D008941:Spindle Apparatus / Q000378:metabolism; D014162:Transfection; D054875:Ubiquitination / Q000502:physiology
D015703:Antigens, CD; C534699:CCNB1 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D061988:Proteasome Inhibitors; C120551:TACC3 protein, human; C577488:CDC20 protein, human; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde