The dual-specificity phosphatase hYVH1 (DUSP12) is a novel modulator of cellular DNA content.
Cell Cycle
; 10(10): 1669-78, 2011 May 15.
Article
em En
| MEDLINE
| ID: mdl-21521943
ABSTRACT
The dual-specificity phosphatase hYVH1 (DUSP12) is an evolutionary conserved phosphatase that also contains a unique zinc-binding domain. Recent evidence suggests that this enzyme plays a role in cell survival and ribosome biogenesis. Here, we report that hYVH1 expression also affects cell cycle progression. Overexpression of hYVH1 caused a significant increase in polyploidy and in the G 2/M cell population, with a subsequent decrease in the G 0/G 1 population. Phosphatase activity is dispensable, while the zinc-binding domain is necessary and sufficient for hYVH1-mediated cell cycle changes. In agreement with this, siRNA-mediated silencing of hYVH1 expression resulted in a dramatic increase in the G 0/G 1 population and susceptibility to cellular senescence. Additionally, mass spectrometry-based methods identified novel hYVH1 phosphorylation sites, including a C-terminal modification at position Ser ( 335) in the zinc-binding domain. Interestingly, phosphorylation at Ser335 regulates subcellular targeting of hYVH1 and augments the hYVH1 G 2/M phenotype. Collectively we demonstrate that hYVH1 is a novel modulator of cell cycle progression; a function mainly mediated by its C-terminal zinc-binding domain.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Fosfatases de Especificidade Dupla
Limite:
Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2011
Tipo de documento:
Article