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The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material

Adelheid Soubry, Katrien Staes UGent, Eef Parthoens UGent, Samuel Noppen UGent, Christophe Stove UGent, Pieter Bogaert UGent, Jolanda van Hengel UGent and Frans Van Roy UGent (2010) PLOS ONE. 5(2).
abstract
Kaiso is a BTB/POZ zinc finger protein known as a transcriptional repressor. It was originally identified through its in vitro association with the Armadillo protein p120ctn. Subcellular localization of Kaiso in cell lines and in normal and cancerous human tissues revealed that its expression is not restricted to the nucleus. In the present study we monitored Kaiso’s subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody. We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex. We analyzed the functions of different domains of Kaiso by visualizing the subcellular distribution of GFP-tagged Kaiso fragments throughout the cell cycle. Our results indicate that two domains are responsible for targeting Kaiso to the centrosomes and microtubules. The first domain, designated SA1 for spindle-associated domain 1, is located in the center of the Kaiso protein and localizes at the spindle microtubules and centrosomes; the second domain, SA2, is an evolutionarily conserved domain situated just before the zinc finger domain and might be responsible for localizing Kaiso towards the centrosomal region. Constructs containing both SA domains and Kaiso’s aminoterminal BTB/POZ domain triggered the formation of abnormal centrosomes. We also observed that overexpression of longer or full-length Kaiso constructs led to mitotic cell arrest and frequent cell death. Knockdown of Kaiso accelerated cell proliferation. Our data reveal a new target for Kaiso at the centrosomes and spindle microtubules during mitosis. They also strongly imply that Kaiso’s function as a transcriptional regulator might be linked to the control of the cell cycle and to cell proliferation in cancer.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GAMMA-TUBULIN COMPLEXES, DNA-BINDING PROTEIN, P120 CATENIN, NUCLEAR-LOCALIZATION, MAMMALIAN-CELLS, CENTROSOMAL PROTEINS, POLE ORGANIZATION, MICROTUBULE-BINDING, CANCER, PARTNER KAISO
journal title
PLOS ONE
PLoS One
volume
5
issue
2
pages
18 pages
publisher
PUBLIC LIBRARY SCIENCE
place of publication
SAN FRANCISCO
Web of Science type
Article
Web of Science id
000274474700006
JCR category
BIOLOGY
JCR impact factor
4.411 (2010)
JCR rank
12/84 (2010)
JCR quartile
1 (2010)
ISSN
1932-6203
DOI
10.1371/journal.pone.0009203
language
English
UGent publication?
yes
classification
A1
copyright statement
I don't know the status of the copyright for this publication
id
883340
handle
http://hdl.handle.net/1854/LU-883340
date created
2010-02-26 09:46:27
date last changed
2012-06-26 14:31:58
@article{883340,
  abstract     = {Kaiso is a BTB/POZ zinc finger protein known as a transcriptional repressor. It was originally identified through its in vitro association with the Armadillo protein p120ctn. Subcellular localization of Kaiso in cell lines and in normal and cancerous human tissues revealed that its expression is not restricted to the nucleus. In the present study we monitored Kaiso{\textquoteright}s subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody. We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex. We analyzed the functions of different domains of Kaiso by visualizing the subcellular distribution of GFP-tagged Kaiso fragments throughout the cell cycle. Our results indicate that two domains are responsible for targeting Kaiso to the centrosomes and microtubules. The first domain, designated SA1 for spindle-associated domain 1, is located in the center of the Kaiso protein and localizes at the spindle microtubules and centrosomes; the second domain, SA2, is an evolutionarily conserved domain situated just before the zinc finger domain and might be responsible for localizing Kaiso towards the centrosomal region. Constructs containing both SA domains and Kaiso{\textquoteright}s aminoterminal BTB/POZ domain triggered the formation of abnormal centrosomes. We also observed that overexpression of longer or full-length Kaiso constructs led to mitotic cell arrest and frequent cell death. Knockdown of Kaiso accelerated cell proliferation. Our data reveal a new target for Kaiso at the centrosomes and spindle microtubules during mitosis. They also strongly imply that Kaiso{\textquoteright}s function as a transcriptional regulator might be linked to the control of the cell cycle and to cell proliferation in cancer.},
  author       = {Soubry, Adelheid and Staes, Katrien and Parthoens, Eef and Noppen, Samuel and Stove, Christophe and Bogaert, Pieter and van Hengel, Jolanda and Van Roy, Frans},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {GAMMA-TUBULIN COMPLEXES,DNA-BINDING PROTEIN,P120 CATENIN,NUCLEAR-LOCALIZATION,MAMMALIAN-CELLS,CENTROSOMAL PROTEINS,POLE ORGANIZATION,MICROTUBULE-BINDING,CANCER,PARTNER KAISO},
  language     = {eng},
  number       = {2},
  pages        = {18},
  publisher    = {PUBLIC LIBRARY SCIENCE},
  title        = {The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material},
  url          = {http://dx.doi.org/10.1371/journal.pone.0009203},
  volume       = {5},
  year         = {2010},
}

Chicago
Soubry, Adelheid, Katrien Staes, Eef Parthoens, Samuel Noppen, Christophe Stove, Pieter Bogaert, Jolanda van Hengel, and Frans Van Roy. 2010. “The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material.” Plos One 5 (2).
APA
Soubry, A., Staes, K., Parthoens, E., Noppen, S., Stove, C., Bogaert, P., van Hengel, J., et al. (2010). The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material. PLOS ONE, 5(2).
Vancouver
1.
Soubry A, Staes K, Parthoens E, Noppen S, Stove C, Bogaert P, et al. The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material. PLOS ONE. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE; 2010;5(2).
MLA
Soubry, Adelheid, Katrien Staes, Eef Parthoens, et al. “The Transcriptional Repressor Kaiso Localizes at the Mitotic Spindle and Is a Constituent of the Pericentriolar Material.” PLOS ONE 5.2 (2010): n. pag. Print.