Control of centrin stability by Aurora A

Kara B. Lukasiewicz, Tammy M. Greenwood, Vivian C. Negron, Amy K. Bruzek, Jeffrey L Salisbury, Wilma L. Lingle

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer.

Original languageEnglish (US)
Article numbere21291
JournalPLoS One
Volume6
Issue number6
DOIs
StatePublished - 2011

Fingerprint

centrosomes
Sulfamethoxazole Drug Combination Trimethoprim
Centrosome
phosphorylation
Phosphorylation
Amplification
serine
phosphotransferases (kinases)
prophase
metaphase
threonine
breast neoplasms
mitosis
Aurora Kinase A
Prophase
Mitotic Index
cells
Protein-Serine-Threonine Kinases
mutation
Metaphase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lukasiewicz, K. B., Greenwood, T. M., Negron, V. C., Bruzek, A. K., Salisbury, J. L., & Lingle, W. L. (2011). Control of centrin stability by Aurora A. PLoS One, 6(6), [e21291]. https://doi.org/10.1371/journal.pone.0021291

Control of centrin stability by Aurora A. / Lukasiewicz, Kara B.; Greenwood, Tammy M.; Negron, Vivian C.; Bruzek, Amy K.; Salisbury, Jeffrey L; Lingle, Wilma L.

In: PLoS One, Vol. 6, No. 6, e21291, 2011.

Research output: Contribution to journalArticle

Lukasiewicz, KB, Greenwood, TM, Negron, VC, Bruzek, AK, Salisbury, JL & Lingle, WL 2011, 'Control of centrin stability by Aurora A', PLoS One, vol. 6, no. 6, e21291. https://doi.org/10.1371/journal.pone.0021291
Lukasiewicz KB, Greenwood TM, Negron VC, Bruzek AK, Salisbury JL, Lingle WL. Control of centrin stability by Aurora A. PLoS One. 2011;6(6). e21291. https://doi.org/10.1371/journal.pone.0021291
Lukasiewicz, Kara B. ; Greenwood, Tammy M. ; Negron, Vivian C. ; Bruzek, Amy K. ; Salisbury, Jeffrey L ; Lingle, Wilma L. / Control of centrin stability by Aurora A. In: PLoS One. 2011 ; Vol. 6, No. 6.
@article{2863b35a589d45038997378ff5b0bb25,
title = "Control of centrin stability by Aurora A",
abstract = "Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer.",
author = "Lukasiewicz, {Kara B.} and Greenwood, {Tammy M.} and Negron, {Vivian C.} and Bruzek, {Amy K.} and Salisbury, {Jeffrey L} and Lingle, {Wilma L.}",
year = "2011",
doi = "10.1371/journal.pone.0021291",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Control of centrin stability by Aurora A

AU - Lukasiewicz, Kara B.

AU - Greenwood, Tammy M.

AU - Negron, Vivian C.

AU - Bruzek, Amy K.

AU - Salisbury, Jeffrey L

AU - Lingle, Wilma L.

PY - 2011

Y1 - 2011

N2 - Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer.

AB - Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer.

UR - http://www.scopus.com/inward/record.url?scp=79959560886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959560886&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0021291

DO - 10.1371/journal.pone.0021291

M3 - Article

C2 - 21731694

AN - SCOPUS:79959560886

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e21291

ER -