Document Detail

Posttranslational nitrotyrosination of alpha-tubulin induces cell cycle arrest and inhibits proliferation of vascular smooth muscle cells.
MedLine Citation:
PMID:  17118269     Owner:  NLM     Status:  MEDLINE    
Hyperproliferation of vascular smooth muscle cells is a hallmark of atherosclerosis and related vascular complications. Microtubules are important for many aspects of mammalian cell responses including growth, migration and signaling. alpha-Tubulin, a component of the microtubule cytoskeleton, is unique amongst cellular proteins in that it undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-tubulin) and re-added (Tyr-tubulin). Whereas the reversible detyrosination/tyrosination cycle of alpha-tubulin has been implicated in regulating various aspects of cell biology, the precise function of this posttranslational modification has remained poorly characterized. Herein, we provide evidence suggesting that alpha-tubulin detyrosination is a required event in the proliferation of vascular smooth muscle cells. Proliferation of rat aortic smooth muscle cells in response to serum was temporally associated with the detyrosination of alpha-tubulin, but not acetylation of alpha-tubulin; Glu-tubulin reached maximal levels between 12 and 18h following cell cycle initiation. Inclusion of 3-nitro-l-tyrosine (NO(2)Tyr) in the culture medium resulted in the selective nitrotyrosination of alpha-tubulin, that was paralleled by decreased elaboration of Glu-tubulin, decreased expression of cyclins A and E, decreased association of the microtubule plus-end binding protein EB1, and inhibited cell proliferation. Nitrotyrosination of alpha-tubulin did not induce necrotic or apoptotic death of rat aortic smooth muscle cells, but instead led to cell cycle arrest at the G(1)/S boundary coincident with decreased DNA synthesis. Collectively, these results suggest that the C-terminus of alpha-tubulin and its detyrosination are functionally important as a molecular switch that regulates cell cycle progression in vascular smooth muscle cells.
Anh D Phung; Karel Soucek; Lukás Kubala; Richart W Harper; J Chloë Bulinski; Jason P Eiserich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  European journal of cell biology     Volume:  85     ISSN:  0171-9335     ISO Abbreviation:  Eur. J. Cell Biol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-22     Completed Date:  2007-02-06     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1241-52     Citation Subset:  IM    
Department of Internal Medicine, University of California, Davis, CA 95616, USA.
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MeSH Terms
Apoptosis / physiology
Cell Cycle / physiology*
Cell Proliferation*
Cells, Cultured
Glutamic Acid / metabolism
Microtubules / physiology
Muscle, Smooth, Vascular / cytology*,  physiology
Protein Processing, Post-Translational / physiology*
Tubulin / metabolism*
Tyrosine / analogs & derivatives*,  metabolism
Grant Support
Reg. No./Substance:
0/Tubulin; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 56-86-0/Glutamic Acid

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