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Inositol polyphosphate multikinase

Sihong Sang, Yao Chen, Qiaofeng Yang, Peng Wang
Timely flowering is critical for successful reproduction and seed yield in plants. A diverse range of regulators have been found to control flowering time in response to environmental and endogenous signals. Among these regulators, FLOWERING LOCUS C (FLC) acts as a central repressor of floral transition by blocking the expression of flowering integrator genes. Here, we report that Arabidopsis inositol polyphosphate multikinase (AtIPK2β) functions in flowering time control by mediating transcriptional regulation of FLC at the chromatin level...
November 17, 2017: Journal of Experimental Botany
Reed B Wickner, Amy C Kelly, Evgeny E Bezsonov, Herman K Edskes
The yeast prions [PSI+] and [URE3] are folded in-register parallel β-sheet amyloids of Sup35p and Ure2p, respectively. In a screen for antiprion systems curing [PSI+] without protein overproduction, we detected Siw14p as an antiprion element. An array of genetic tests confirmed that many variants of [PSI+] arising in the absence of Siw14p are cured by restoring normal levels of the protein. Siw14p is a pyrophosphatase specifically cleaving the β phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5), suggesting that increased levels of this or some other inositol polyphosphate favors [PSI+] propagation...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
Ciro D Cordeiro, Adolfo Saiardi, Roberto Docampo
Inositol pyrophosphates are novel signaling molecules possessing high-energy pyrophosphate bonds and involved in a number of biological functions. Here, we report the correct identification and characterization of the kinases involved in the inositol pyrophosphate biosynthetic pathway in Trypanosoma brucei: inositol polyphosphate multikinase (TbIPMK), inositol pentakisphosphate 2-kinase (TbIP5K) and inositol hexakisphosphate kinase (TbIP6K). TbIP5K and TbIP6K were not identifiable by sequence alone and their activities were validated by enzymatic assays with the recombinant proteins or by their complementation of yeast mutants...
October 2017: Molecular Microbiology
Eunha Kim, Hyoungjoon Ahn, Min Gyu Kim, Haein Lee, Seyun Kim
The inositol polyphosphates are a group of multifunctional signaling metabolites whose synthesis is catalyzed by a family of inositol kinases that are evolutionarily conserved from yeast to humans. Inositol polyphosphate multikinase (IPMK) was first identified as a subunit of the arginine-responsive transcription complex in budding yeast. In addition to its role in the production of inositol tetrakis- and pentakisphosphates (IP4 and IP5), IPMK also exhibits phosphatidylinositol 3-kinase (PI3-kinase) activity...
May 31, 2017: Molecules and Cells
Jianrong Li, Bing Zhang, Tianyu Ma, Honggang Wang, Biao Zhang, Qilin Yu, Mingchun Li
Inositol polyphosphates are a family of inositol derivatives and ubiquitously distributed in various organisms. Their generation is catalyzed by inositol polyphosphate multikinases, which play essential roles in abundant cellular processes. However, little is known about the kinds and functions of inositol polyphosphate multikinases in the important fungal pathogen, C. albicans. In this study, we identified a C. albicans inositol polyphosphate multikinase, Ipk2. This kinase shares the conserved IPK domain and localizes in the nucleus...
August 2017: Mycopathologia
Eunha Kim, Jiyoon Beon, Seulgi Lee, Seung Ju Park, Hyoungjoon Ahn, Min Gyu Kim, Jeong Eun Park, Wooseob Kim, Jae-Min Yuk, Suk-Jo Kang, Seung-Hyo Lee, Eun-Kyeong Jo, Rho Hyun Seong, Seyun Kim
Toll-like receptor (TLR) signaling is tightly controlled to protect hosts from microorganisms while simultaneously preventing uncontrolled immune responses. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a critical mediator of TLR signaling, but the precise mechanism of how TRAF6 protein stability is strictly controlled still remains obscure. We show that myeloid-specific deletion of inositol polyphosphate multikinase (IPMK), which has both inositol polyphosphate kinase activities and noncatalytic signaling functions, protects mice against polymicrobial sepsis and lipopolysaccharide-induced systemic inflammation...
April 2017: Science Advances
Louis de Mestier, Eric Pasmant, Clémence Fleury, Hedia Brixi, Pierre Sohier, Thomas Féron, Marie-Danièle Diebold, Eric Clauser, Guillaume Cadiot
BACKGROUND: Familial small-intestine neuroendocrine tumors (SI-NETs) are an exceptional inherited entity. Underlying predisposing mechanisms are unelucidated, but inositol polyphosphate multikinase (IPMK) gene alterations might promote their tumorigenesis. METHODS: A retrospective-prospective nationwide cohort was constituted, by including patients with proven SI-NETs and at least one relative with the same disease. We performed constitutional and somatic IPMK sequencing, and somatic DNA comparative genomic hybridization (CGH)...
January 2017: Digestive and Liver Disease
Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Anna Maria Billi, Lucia Manzoli, Sara Mongiorgi, Stefano Ratti, James A McCubrey, Pann-Ghill Suh, Lucio Cocco, Matilde Y Follo
Phosphoinositide-phospholipase C-β1 (PLC-β1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation and osteogenesis. During myogenic differentiation of murine C2C12 myoblasts, PLC-β1 signaling pathway involves the Inositol Polyphosphate Multikinase (IPMK) and β-catenin as downstream effectors. By means of c-jun binding to cyclin D3 promoter, the activation of PLC-β1 pathway determines cyclin D3 accumulation. However, osteogenesis requires PLC-β1 expression and up-regulation but it does not affect cyclin D3 levels, suggesting that the two processes require the activation of different mediators...
October 18, 2016: Advances in Biological Regulation
Giulia Ramazzotti, Anna Maria Billi, Lucia Manzoli, Cristina Mazzetti, Alessandra Ruggeri, Christophe Erneux, Seyun Kim, Pann-Ghill Suh, Lucio Cocco, Irene Faenza
In previous studies, we have reported that phospholipase C (PLC)-β1 plays a crucial role in myogenic differentiation and we determined the importance of its catalytic activity for the initiation of this process. Here we define the effectors that take part to its signaling pathway. We show that the Inositol Polyphosphate Multikinase (IPMK) is able to promote myogenic differentiation since its overexpression determines the up-regulation of several myogenic markers. Moreover, we demonstrate that IPMK activates the same cyclin D3 promoter region targeted by PLC-β1 and that IPMK-induced promoter activation relies upon c-jun binding to the promoter, as we have shown previously for PLC-β1...
December 20, 2016: Oncotarget
Igor Cestari, Paige Haas, Nilmar Silvio Moretti, Sergio Schenkman, Ken Stuart
Kinetoplastids cause Chagas disease, human African trypanosomiasis, and leishmaniases. Current treatments for these diseases are toxic and inefficient, and our limited knowledge of drug targets and inhibitors has dramatically hindered the development of new drugs. Here we used a chemogenetic approach to identify new kinetoplastid drug targets and inhibitors. We conditionally knocked down Trypanosoma brucei inositol phosphate (IP) pathway genes and showed that almost every pathway step is essential for parasite growth and infection...
May 19, 2016: Cell Chemical Biology
M Merced Malabanan, Raymond D Blind
Inositol polyphosphate multikinase (IPMK, ipk2, Arg(82), ArgRIII) is an inositide kinase with unusually flexible substrate specificity and the capacity to partake in many functional protein-protein interactions (PPIs). By merging these two activities, IPMK is able to execute gene regulatory functions that are very unique and only now beginning to be recognized. In this short review, we present a brief history of IPMK, describe the structural biology of the enzyme and highlight a few recent discoveries that have shed more light on the role IPMK plays in inositide metabolism, nuclear signalling and transcriptional regulation...
February 2016: Biochemical Society Transactions
Eunha Kim, Jiyoon Beon, Seulgi Lee, Jina Park, Seyun Kim
Inositol-derived metabolites (e.g., phosphoinositides and inositol polyphosphates) are key second messengers that are essential for controlling a wide range of cellular events. Inositol polyphosphate multikinase (IPMK) exhibits complex catalytic activities that eventually yield water-soluble inositol polyphosphates (e.g., IP4 and IP5) and lipid-bound phosphatidylinositol 3,4,5-trisphosphate. A series of recent studies have suggested that IPMK may be a multifunctional regulator in the nucleus of mammalian cells...
May 2016: Advances in Biological Regulation
Ishrat Ahmed, Juan I Sbodio, Maged M Harraz, Richa Tyagi, Jonathan C Grima, Lauren K Albacarys, Maimon E Hubbi, Risheng Xu, Seyun Kim, Bindu D Paul, Solomon H Snyder
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...
August 4, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yoshitatsu Sei, Xilin Zhao, Joanne Forbes, Silke Szymczak, Qing Li, Apurva Trivedi, Mark Voellinger, Grishma Joy, Jianying Feng, Millie Whatley, MaryPat Sussex Jones, Ursula L Harper, Stephen J Marx, Aradhana M Venkatesan, Settara C Chandrasekharappa, Mark Raffeld, Martha M Quezado, Adeline Louie, Clara C Chen, Ramona M Lim, Richa Agarwala, Alejandro A Schäffer, Marybeth S Hughes, Joan E Bailey-Wilson, Stephen A Wank
BACKGROUND & AIMS: Small intestinal carcinoids are rare and difficult to diagnose and patients often present with advanced incurable disease. Although the disease occurs sporadically, there have been reports of family clusters. Hereditary small intestinal carcinoid has not been recognized and genetic factors have not been identified. We performed a genetic analysis of families with small intestinal carcinoids to establish a hereditary basis and find genes that might cause this cancer...
July 2015: Gastroenterology
Aleksey Porollo, Thomas M Sesterhenn, Margaret S Collins, Jeffrey A Welge, Melanie T Cushion
UNLABELLED: In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P. murina, and P. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The underrepresentation of amino acid metabolism pathways compared to those in S. pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed for P...
November 4, 2014: MBio
Sookhee Bang, Yong Chen, Rexford S Ahima, Sangwon F Kim
Metformin is a biguanide drug that is widely prescribed for type 2 diabetes. Metformin suppresses hepatic gluconeogenesis and increases fatty acid oxidation. Although studies have suggested that metformin acts, at least in part, via activation of the liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway, the specific molecular mechanisms underlying metformin's regulation of glucose and lipid metabolism have not been well delineated. Recently, we have shown that inositol polyphosphate multikinase (IPMK) plays an important role in cellular energy metabolism and glucose-mediated AMPK regulation...
July 2014: Molecular Endocrinology
Bernadett Kolozsvari, Federica Parisi, Adolfo Saiardi
The polymer inorganic polyP (polyphosphate) and inositol phosphates, such as IP6 (inositol hexakisphosphate; also known as phytic acid), share many biophysical features. These similarities must be attributed to the phosphate groups present in these molecules. Given the ability of polyP to modify the excitation-emission spectra of DAPI we decided to investigate whether inositol phosphates possess the same property. We discovered that DAPI-IP6 complexes emit at approximately 550 nm when excited with light of wavelength 410-420 nm...
June 15, 2014: Biochemical Journal
Eunha Kim, Richa Tyagi, Joo-Young Lee, Jina Park, Young-Ran Kim, Jiyoon Beon, Po Yu Chen, Jiyoung Y Cha, Solomon H Snyder, Seyun Kim
Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes...
December 3, 2013: Proceedings of the National Academy of Sciences of the United States of America
Vihandha O Wickramasinghe, Jane M Savill, Sreenivas Chavali, Asta B Jonsdottir, Eeson Rajendra, Tamara Grüner, Ronald A Laskey, M Madan Babu, Ashok R Venkitaraman
Messenger RNA (mRNA) export from the nucleus is essential for eukaryotic gene expression. Here we identify a transcript-selective nuclear export mechanism affecting certain human transcripts, enriched for functions in genome duplication and repair, controlled by inositol polyphosphate multikinase (IPMK), an enzyme catalyzing inositol polyphosphate and phosphoinositide turnover. We studied transcripts encoding RAD51, a protein essential for DNA repair by homologous recombination (HR), to characterize the mechanism underlying IPMK-regulated mRNA export...
September 26, 2013: Molecular Cell
Risheng Xu, Bindu D Paul, Dani R Smith, Richa Tyagi, Feng Rao, A Basit Khan, Daniel J Blech, M Scott Vandiver, Maged M Harraz, Prasun Guha, Ishrat Ahmed, Nilkantha Sen, Michela Gallagher, Solomon H Snyder
Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters...
October 1, 2013: Proceedings of the National Academy of Sciences of the United States of America
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