TY - JOUR
T1 - A Novel Inositol Pyrophosphate Phosphatase in Saccharomyces cerevisiae
T2 - Siw14 Protein selectively cleaves the β-Phosphate from 5-Diphosphoinositol Pentakisphosphate (5PP-IP5)
AU - Steidle, Elizabeth A.
AU - Chong, Lucy S.
AU - Wu, Mingxuan
AU - Crooke, Elliott
AU - Fiedler, Dorothea
AU - Resnick, Adam C.
AU - Rolfes, Ronda J.
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/3/25
Y1 - 2016/3/25
N2 - Inositol pyrophosphates are high energy signaling molecules involved in cellular processes, such as energetic metabolism, telomere maintenance, stress responses, and vesicle trafficking, and can mediate protein phosphorylation. Although the inositol kinases underlying inositol pyrophosphate biosynthesis are well characterized, the phosphatases that selectively regulate their cellular pools are not fully described. The diphosphoinositol phosphate phosphohydrolase enzymes of the Nudix protein family have been demonstrated to dephosphorylate inositol pyrophosphates; however, the Saccharomyces cerevisiae homolog Ddp1 prefers inorganic polyphosphate over inositol pyrophosphates. We identified a novel phosphatase of the recently discovered atypical dual specificity phosphatase family as a physiological inositol pyrophosphate phosphatase. Purified recombinant Siw14 hydrolyzes the β-phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5 or IP7) in vitro. In vivo, siw14δ yeast mutants possess increased IP7 levels, whereas heterologous SIW14 overexpression eliminates IP7 from cells. IP7 levels increased proportionately when siw14δ was combined with ddp1δ or vip1δ, indicating independent activity by the enzymes encoded by these genes. We conclude that Siw14 is a physiological phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7 isoform 5PPIP5 to IP6.
AB - Inositol pyrophosphates are high energy signaling molecules involved in cellular processes, such as energetic metabolism, telomere maintenance, stress responses, and vesicle trafficking, and can mediate protein phosphorylation. Although the inositol kinases underlying inositol pyrophosphate biosynthesis are well characterized, the phosphatases that selectively regulate their cellular pools are not fully described. The diphosphoinositol phosphate phosphohydrolase enzymes of the Nudix protein family have been demonstrated to dephosphorylate inositol pyrophosphates; however, the Saccharomyces cerevisiae homolog Ddp1 prefers inorganic polyphosphate over inositol pyrophosphates. We identified a novel phosphatase of the recently discovered atypical dual specificity phosphatase family as a physiological inositol pyrophosphate phosphatase. Purified recombinant Siw14 hydrolyzes the β-phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5 or IP7) in vitro. In vivo, siw14δ yeast mutants possess increased IP7 levels, whereas heterologous SIW14 overexpression eliminates IP7 from cells. IP7 levels increased proportionately when siw14δ was combined with ddp1δ or vip1δ, indicating independent activity by the enzymes encoded by these genes. We conclude that Siw14 is a physiological phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7 isoform 5PPIP5 to IP6.
UR - http://www.scopus.com/inward/record.url?scp=84964723123&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964723123&partnerID=8YFLogxK
U2 - 10.1074/jbc.M116.714907
DO - 10.1074/jbc.M116.714907
M3 - Article
C2 - 26828065
AN - SCOPUS:84964723123
SN - 0021-9258
VL - 291
SP - 6772
EP - 6783
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -