Pax6p46 binds chromosomes in the pericentromeric region and induces a mitosis defect when overexpressed.
Invest. Ophthalmol. Vis. Sci.. 2007-12-01; 48(12): 5408
DOI: 10.1167/iovs.07-0413
Lire sur PubMed
1. Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5408-19.
Pax6p46 binds chromosomes in the pericentromeric region and induces a mitosis
defect when overexpressed.
Zaccarini R(1), Cordelières FP, Martin P, Saule S.
Author information:
(1)Institut Curie, Centre National de la Recherche Scientifique (CNRS) UMR 146,
Centre Universitaire Orsay, Orsay, France.
PURPOSE: Haploinsufficiency and overexpression of the Pax6 gene are responsible
for defective central nervous system development. The purpose of the current work
was to identify and characterize a new potential role for the Pax6 transcription
factor in cellular proliferation in addition to its role at the level of gene
expression.
METHODS: Expression vectors encoding tagged Pax6p46 protein were used to observe
directly protein localization during the cell cycle in cells lines. Three
dimensional (3-D) fluorescence microscopy imaging was used to observe in vivo
mitotic progression and chromosome dynamics to define the mitotic step affected
by p46DsRed as well as to validate endogenous p46 localization on chromosomes in
quail retinal cells. Video imaging was used to identify the precise moment of
onset of effects related to p46 overexpression in living cells. A pulldown assay
in HEK cells was used to identify a specific partner of p46.
RESULTS: Pax6p46 protein in transfected cells is localized on the chromosomes,
predominantly in a pericentromeric area, and its localization changes as mitosis
progresses. Overexpression of p46 protein induces incomplete chromatid
separation, resulting in defective mitosis at the onset of the anaphase. A
physical interaction between p46 and ESPL1 was identified.
CONCLUSIONS: The results suggest that Pax6 exerts an effect on mitosis through
protein-protein interactions with proteins localized on chromosomes. Supported by
the observation that p46 interacts with separase, an enzyme required for
chromatid separation, the authors propose that this interaction is responsible
for the mitosis defect observed in cells overexpressing Pax6.
DOI: 10.1167/iovs.07-0413
PMID: 18055787 [Indexed for MEDLINE]