Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification.
The potential tumor suppressor antizyme and its endogenous inhibitor (antizyme inhibitor, AZI) have been implicated in the ubiquitin-independent proteasomal degradation of proteins involved in cell proliferation as well as in the regulation of polyamine levels. We show here that both antizyme and AZI concentrate at centrosomes and that antizyme preferentially associates with the maternal centriole. Interestingly, alterations in the levels of these proteins have opposing effects on centrosomes. Depletion of antizyme in various cell lines and primary cells leads to centrosome overduplication, whereas overexpression of antizyme reduces numerical centrosome abnormalities. Conversely, silencing of the antizyme inhibitor, AZI, results in a decrease of numerical centrosome abnormalities, whereas overexpression of AZI leads to centrosome overduplication. We further show that the numerical centrosome abnormalities are due to daughter centriole amplification. In summary, our results demonstrate that alterations in the antizyme/AZI balance cause numerical centrosomal defects and suggest a role for ubiquitin-independent proteasomal degradation in centrosome duplication.
Program in Vascular Biology, Children's Hospital Boston, Boston, MA, USA.
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U
Mangold
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Hayakawa
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M
Coughlin
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Münger
B R
BR
Zetter
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D025801:Ubiquitin / Q000378:metabolism
C484011:AZIN1 protein, human; D002352:Carrier Proteins; D011506:Proteins; D025801:Ubiquitin; C031017:ornithine decarboxylase antizyme; D046988:Proteasome Endopeptidase Complex