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Deubiquitination of γ-tubulin by BAP1 prevents chromosome instability in breast cancer cells.

Zarrizi, Reihaneh LU ; Menard, Julien LU ; Belting, Mattias LU and Massoumi, Ramin LU (2014) In Cancer Research 74(22). p.6499-6508
Abstract
Microtubule nucleation requires the γ-tubulin ring complex, and during the M phase (mitosis) this complex accumulates at the centrosome to support mitotic spindle formation. The post-translational modification of γ-tubulin through ubiquitination is vital for regulating microtubule nucleation and centrosome duplication. Blocking the BRCA1/BARD1-dependent ubiquitination of γ-tubulin causes centrosome amplification. In the present study, we identified BRCA1 associated protein-1 (BAP1) as a deubiquitination enzyme for γ-tubulin. BAP1 was downregulated in metastatic adenocarcinoma breast cell lines compared to non-cancerous human breast epithelial cells. Furthermore, low expression of BAP1 was associated with reduced overall survival of breast... (More)
Microtubule nucleation requires the γ-tubulin ring complex, and during the M phase (mitosis) this complex accumulates at the centrosome to support mitotic spindle formation. The post-translational modification of γ-tubulin through ubiquitination is vital for regulating microtubule nucleation and centrosome duplication. Blocking the BRCA1/BARD1-dependent ubiquitination of γ-tubulin causes centrosome amplification. In the present study, we identified BRCA1 associated protein-1 (BAP1) as a deubiquitination enzyme for γ-tubulin. BAP1 was downregulated in metastatic adenocarcinoma breast cell lines compared to non-cancerous human breast epithelial cells. Furthermore, low expression of BAP1 was associated with reduced overall survival of breast cancer patients. Reduced expression of BAP1 in breast cancer cell lines was associated with mitotic abnormalities. Importantly, rescue experiments including expression of full length but not the catalytic mutant of BAP1 reduced ubiquitination of γ-tubulin and prevented mitotic defects. Our study uncovers a new mechanism for BAP1 involved in deubiquitination of γ-tubulin, which is required to prevent abnormal mitotic spindle formation and genome instability. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
74
issue
22
pages
6499 - 6508
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:25228651
  • wos:000345130500013
  • scopus:84918499999
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-14-0221
language
English
LU publication?
yes
id
d7d829de-ad5b-4ebf-b24b-60753adce358 (old id 4691389)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25228651?dopt=Abstract
date added to LUP
2014-10-07 19:26:09
date last changed
2017-10-01 03:05:57
@article{d7d829de-ad5b-4ebf-b24b-60753adce358,
  abstract     = {Microtubule nucleation requires the γ-tubulin ring complex, and during the M phase (mitosis) this complex accumulates at the centrosome to support mitotic spindle formation. The post-translational modification of γ-tubulin through ubiquitination is vital for regulating microtubule nucleation and centrosome duplication. Blocking the BRCA1/BARD1-dependent ubiquitination of γ-tubulin causes centrosome amplification. In the present study, we identified BRCA1 associated protein-1 (BAP1) as a deubiquitination enzyme for γ-tubulin. BAP1 was downregulated in metastatic adenocarcinoma breast cell lines compared to non-cancerous human breast epithelial cells. Furthermore, low expression of BAP1 was associated with reduced overall survival of breast cancer patients. Reduced expression of BAP1 in breast cancer cell lines was associated with mitotic abnormalities. Importantly, rescue experiments including expression of full length but not the catalytic mutant of BAP1 reduced ubiquitination of γ-tubulin and prevented mitotic defects. Our study uncovers a new mechanism for BAP1 involved in deubiquitination of γ-tubulin, which is required to prevent abnormal mitotic spindle formation and genome instability.},
  author       = {Zarrizi, Reihaneh and Menard, Julien and Belting, Mattias and Massoumi, Ramin},
  issn         = {1538-7445},
  language     = {eng},
  number       = {22},
  pages        = {6499--6508},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Deubiquitination of γ-tubulin by BAP1 prevents chromosome instability in breast cancer cells.},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-14-0221},
  volume       = {74},
  year         = {2014},
}