The Dual-Specificity Protein Phosphatase Yvh1p Regulates Sporulation, Growth, and Glycogen Accumulation Independently of Catalytic Activity in Saccharomyces cerevisiae via the Cyclic AMP-Dependent Protein Kinase Cascade

Abstract

Yvh1p, a dual-specific protein phosphatase induced specifically by nitrogen starvation, regulates cell growth as well as initiation and completion of sporulation. We demonstrate that yvh1 disruption mutants are also unable to accumulate glycogen in stationary phase. A catalytically inactive variant of yvh1 (C117S) and a DNA fragment encoding only the Yvh1p C-terminal 159 amino acids (which completely lacks the phosphatase domain) complement all three phenotypes as well as the wild-type allele; no complementation occurs with a fragment encoding only the C-terminal 74 amino acids. These observations argue that phosphatase activity is not required for the Yvh1p functions we measured. Mutations which decrease endogenous cyclic AMP (cAMP) levels partially suppress the sporulation and glycogen accumulation defects. In addition, reporter gene expression supported by a DRR2 promoter fragment, containing two stress response elements known to respond to cAMP-protein kinase A, decreases in a yvh1 disruption mutant. Therefore, our results identify three cellular processes that both require Yvh1p and respond to alterations in cAMP, and they lead us to suggest that Yvh1p may be a participant in and/or a contributor to regulation of the cAMP-dependent protein kinase cascade. The fact that decreasing the levels of cAMP alleviates the need for Yvh1p function supports this suggestion.

The dual-specificity phosphatase hYVH1 (DUSP12) is a novel modulator of cellular DNA content

“…This finding is reminiscent of studies in yeast where the phosphatase activity seems dispensable for complementing various cell growth defects including sporulation and ribosome biogenesis, when the yvh1 gene is deleted while the zinc-binding domain is required. 4,8,12,13 While the precise function of this domain remains unknown, we predict that it serves as an interaction module and are currently performing mass spectrometry-based experiments aimed at identifying biomolecules (proteins and/or nucleic acids) that associate with this domain in a cell cycle-dependent manner.…”

“…In yeast, the C-terminal zinc-binding domain is able to complement the slow-growth phenotype of a yvh1 deletion, 8,16 rescue the 60S export defect 12,13,16 and is necessary for glycogen accumulation, growth and spore maturation. 8 In humans, this domain can function as a redox sensor and is necessary for the cytoprotective function of hYVH1. 14,17 We therefore tested the overexpression of the zinc-binding domain as well hYVH1 remains a poorly understood phosphatase especially regarding how its activities are regulated in the cell.…”

“…5 Additional phenotypes due to deletion of YVH1 in yeast include defects in glycogen metabolism and spore maturation. 8 A yeast two-hybrid screen identified YPH1 (yeast pescadillo homolog, Nop7) as a yeast YVH1-interacting partner. 9 Nop7 is required for multiple activities during 60S ribosomal synthesis.…”

A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida albicans

“…In the model yeast Saccharomyces cerevisiae, YVH1, one of the DSPs, was first identified as a vaccinia VH1 homologue (Guan et al, 1992). Deletion of YVH1 in S. cerevisiae causes defects in vegetative growth (particularly at lower temperatures), sporulation and glycogen accumulation, and transcription of YVH1 is induced by low temperature and nitrogen starvation (Beeser & Cooper, 2000;Guan et al, 1992;Park et al, 1996;Sakumoto et al, 1999Sakumoto et al, , 2001). However, even in S. cerevisiae, the exact function of YVH1 remains to be elucidated.…”

Emerging Roles of Atypical Dual Specificity Phosphatases in Cancer

“…YVH1 transcription is up-regulated by nitrogen starvation and low temperatures and yvh1Δ yeast strains exhibit a severe growth phenotype, display defects in sporulation, glycogen accumulation, and ribosome biogenesis [74][75][76][77][78]. Expression of the Yvh1p CRD domain in isolation was able to suppress all the mutant phenotypes of yvh1Δ strains, suggesting that neither phosphatase activity nor the N-terminal phosphatase domain is required for its cellular function in yeast [76]. The DUSP12 CRD has been alternatively described as a LIMdomain, a zinc-finger and a RING-variant domain due to its ability to coordinate zinc, but how it contributes to biological function is not clear [61].…”