title: The dual-specificity phosphatase hYVH1 (DUSP12) is a novel modulator of cellular DNA content.
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.
authors.affiliation: University of Windsor, Windsor, Ontario, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Kozarova
authors.forename: John W
authors.initials: JW
authors.lastname: Hudson
authors.forename: Panayiotis O
authors.initials: PO
authors.lastname: Vacratsis
mesh_terms: D002455:Cell Division; D002460:Cell Line; D016922:Cellular Senescence; D004247:DNA / Q000378:metabolism*; D054637:Dual-Specificity Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase; D006801:Humans; D010766:Phosphorylation; D011123:Polyploidy; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
chemical_list: D034741:RNA, Small Interfering; D004247:DNA; C489855:dual specificity phosphatase 12; D054637:Dual-Specificity Phosphatases; D015032:Zinc