scholarly journals Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

2013 ◽  
Vol 6 (269) ◽  
pp. ra22-ra22 ◽  
Author(s):  
R. Xu ◽  
N. Sen ◽  
B. D. Paul ◽  
A. M. Snowman ◽  
F. Rao ◽  
...  
Keyword(s):  
Cell Death ◽  
Inositol Polyphosphate ◽  
Inositol Polyphosphate Multikinase

scholarly journals Huntington’s disease: Neural dysfunction linked to inositol polyphosphate multikinase

2015 ◽  
Vol 112 (31) ◽  
pp. 9751-9756 ◽  
Author(s):  
Ishrat Ahmed ◽  
Juan I. Sbodio ◽  
Maged M. Harraz ◽  
Richa Tyagi ◽  
Jonathan C. Grima ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Kinase Activity ◽  
Inositol Phosphate ◽  
Cell Model ◽  
Inositol Polyphosphate ◽  
Interacting Protein ◽  
Lipid Kinase ◽  
Inositol Polyphosphate Multikinase ◽  
Neural Dysfunction

Huntington’s disease (HD) is a progressive neurodegenerative disease caused by a glutamine repeat expansion in mutant huntingtin (mHtt). Despite the known genetic cause of HD, the pathophysiology of this disease remains to be elucidated. Inositol polyphosphate multikinase (IPMK) is an enzyme that displays soluble inositol phosphate kinase activity, lipid kinase activity, and various noncatalytic interactions. We report a severe loss of IPMK in the striatum of HD patients and in several cellular and animal models of the disease. This depletion reflects mHtt-induced impairment of COUP-TF-interacting protein 2 (Ctip2), a striatal-enriched transcription factor for IPMK, as well as alterations in IPMK protein stability. IPMK overexpression reverses the metabolic activity deficit in a cell model of HD. IPMK depletion appears to mediate neural dysfunction, because intrastriatal delivery of IPMK abates the progression of motor abnormalities and rescues striatal pathology in transgenic murine models of HD.

scholarly journals Inositol Polyphosphate Multikinase (IPMK), a Gene Coding for a Potential Moonlighting Protein, Contributes to Human Female Longevity

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 125 ◽  
Author(s):  
Francesco De Rango ◽  
Paolina Crocco ◽  
Francesca Iannone ◽  
Adolfo Saiardi ◽  
Giuseppe Passarino ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Inositol Phosphates ◽  
Nutrient Sensing ◽  
Human Longevity ◽  
Cell Physiology ◽  
Inositol Polyphosphate ◽  
Moonlighting Protein ◽  
Key Enzyme ◽  
Female Longevity ◽  
Inositol Polyphosphate Multikinase

Biogerontological research highlighted a complex and dynamic connection between aging, health and longevity, partially determined by genetic factors. Multifunctional proteins with moonlighting features, by integrating different cellular activities in the space and time, may explain part of this complexity. Inositol Polyphosphate Multikinase (IPMK) is a potential moonlighting protein performing multiple unrelated functions. Initially identified as a key enzyme for inositol phosphates synthesis, small messengers regulating many aspects of cell physiology, IPMK is now implicated in a number of metabolic pathways affecting the aging process. IPMK regulates basic transcription, telomere homeostasis, nutrient-sensing, metabolism and oxidative stress. Here, we tested the hypothesis that the genetic variability of IPMK may affect human longevity. Single-SNP (single nuclear polymorphism), haplotype-based association tests as well as survival analysis pointed to the relevance of six out of fourteen genotyped SNPs for female longevity. In particular, haplotype analysis refined the association highlighting two SNPs, rs2790234 and rs6481383, as major contributing variants for longevity in women. Our work, the first to investigate the association between variants of IPMK and longevity, supports IPMK as a novel gender-specific genetic determinant of human longevity, playing a role in the complex network of genetic factors involved in human survival.

scholarly journals Inositol polyphosphate multikinase is a metformin target that regulates cell migration

2019 ◽  
Vol 33 (12) ◽  
pp. 14137-14146 ◽  
Author(s):  
Becky Tu-Sekine ◽  
Abinash Padhi ◽  
Sunghee Jin ◽  
Srivathsan Kalyan ◽  
Karanpreet Singh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Inositol Polyphosphate ◽  
Inositol Polyphosphate Multikinase

scholarly journals Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB

2011 ◽  
Vol 108 (4) ◽  
pp. 1391-1396 ◽  
Author(s):  
D. Maag ◽  
M. J. Maxwell ◽  
D. A. Hardesty ◽  
K. L. Boucher ◽  
N. Choudhari ◽  
...  
Keyword(s):  
Pi3 Kinase ◽  
Inositol Polyphosphate ◽  
Inositol Polyphosphate Multikinase
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