2006
Phung, Anh D.; Soucek, Karel; Kubala, Lukás; Harper, Richart W.; Bulinski, J. Chloë; Eiserich, Jason P.
Posttranslational nitrotyrosination of alpha-tubulin induces cell cycle arrest and inhibits proliferation of vascular smooth muscle cells. Journal Article
In: European journal of cell biology, vol. 85, no. 12, pp. 1241–1252, 2006, ISSN: 0171-9335, (Place: Germany).
Abstract | Links | BibTeX | Tags: *Cell Proliferation, Animals, Apoptosis/physiology, Cell Cycle/*physiology, Cells, Cultured, Glutamic Acid/metabolism, Microtubules/physiology, Muscle, Post-Translational/*physiology, Protein Processing, Rats, Smooth, Tubulin/*metabolism, Tyrosine/*analogs & derivatives/metabolism, Vascular/*cytology/physiology
@article{phung_posttranslational_2006,
title = {Posttranslational nitrotyrosination of alpha-tubulin induces cell cycle arrest and inhibits proliferation of vascular smooth muscle cells.},
author = {Anh D. Phung and Karel Soucek and Lukás Kubala and Richart W. Harper and J. Chloë Bulinski and Jason P. Eiserich},
doi = {10.1016/j.ejcb.2006.05.016},
issn = {0171-9335},
year = {2006},
date = {2006-12-01},
journal = {European journal of cell biology},
volume = {85},
number = {12},
pages = {1241–1252},
abstract = {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.},
note = {Place: Germany},
keywords = {*Cell Proliferation, Animals, Apoptosis/physiology, Cell Cycle/*physiology, Cells, Cultured, Glutamic Acid/metabolism, Microtubules/physiology, Muscle, Post-Translational/*physiology, Protein Processing, Rats, Smooth, Tubulin/*metabolism, Tyrosine/*analogs & derivatives/metabolism, Vascular/*cytology/physiology},
pubstate = {published},
tppubtype = {article}
}
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.