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Nuclear functions of an inositol pol...
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Odom, Audrey Ragan.
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Nuclear functions of an inositol polyphosphate kinase pathway.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
Nuclear functions of an inositol polyphosphate kinase pathway./
Author:
Odom, Audrey Ragan.
Description:
214 p.
Notes:
Source: Dissertation Abstracts International, Volume: 63-09, Section: B, page: 4034.
Contained By:
Dissertation Abstracts International63-09B.
Subject:
Biology, Cell. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3063197
ISBN:
0493819428
Nuclear functions of an inositol polyphosphate kinase pathway.
Odom, Audrey Ragan.
Nuclear functions of an inositol polyphosphate kinase pathway.
- 214 p.
Source: Dissertation Abstracts International, Volume: 63-09, Section: B, page: 4034.
Thesis (Ph.D.)--Duke University, 2002.
Phosphoinositide (PI) signaling is pivotal to cellular processes ranging from proliferation and differentiation to apoptosis. Classically, activation of phospholipase C releases the second messenger IP<sub>3</sub> to mediate intracellular calcium release. IP<sub>3</sub> is also a metabolic precursor to higher phosphorylated inositol phosphates, such as IP<sub>4</sub>, IP<sub>5</sub>, and IP<sub>6</sub>, many of which have uncharacterized cellular functions. This work defines the metabolic pathway for IP<sub>6</sub> synthesis through genetic and biochemical studies in the budding yeast, <italic>Saccharomyces cerevisiae</italic>. The action of phospholipase C in yeast produces IP<sub> 3</sub>, which is then sequentially phosphorylated by two inositol polyphosphate kinases to produce IP<sub>4</sub>, IP<sub>5</sub>, and ultimately IP<sub> 6</sub>. Genetic interactions with phospholipase C, these two inositol phosphate kinases, and the essential mRNA export factor Gle1 have established a role for IP<sub>6</sub> production in efficient nucleocytoplasmic transport of messenger RNA.
ISBN: 0493819428Subjects--Topical Terms:
1017686
Biology, Cell.
Nuclear functions of an inositol polyphosphate kinase pathway.
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Nuclear functions of an inositol polyphosphate kinase pathway.
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214 p.
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Source: Dissertation Abstracts International, Volume: 63-09, Section: B, page: 4034.
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Supervisor: John D. York.
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Thesis (Ph.D.)--Duke University, 2002.
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Phosphoinositide (PI) signaling is pivotal to cellular processes ranging from proliferation and differentiation to apoptosis. Classically, activation of phospholipase C releases the second messenger IP<sub>3</sub> to mediate intracellular calcium release. IP<sub>3</sub> is also a metabolic precursor to higher phosphorylated inositol phosphates, such as IP<sub>4</sub>, IP<sub>5</sub>, and IP<sub>6</sub>, many of which have uncharacterized cellular functions. This work defines the metabolic pathway for IP<sub>6</sub> synthesis through genetic and biochemical studies in the budding yeast, <italic>Saccharomyces cerevisiae</italic>. The action of phospholipase C in yeast produces IP<sub> 3</sub>, which is then sequentially phosphorylated by two inositol polyphosphate kinases to produce IP<sub>4</sub>, IP<sub>5</sub>, and ultimately IP<sub> 6</sub>. Genetic interactions with phospholipase C, these two inositol phosphate kinases, and the essential mRNA export factor Gle1 have established a role for IP<sub>6</sub> production in efficient nucleocytoplasmic transport of messenger RNA.
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We have also found that the dual-specificity IP<sub>3</sub>/IP<sub>4 </sub> kinase of this pathway, Ipk2, is identical to the transcriptional regulator Arg82 and is localized to the nucleus of the cell. Ipk2 protein, but not its kinase activity or inositol phosphate products, is important for assembly of and transcriptional repression through a particular transcriptional complex. Importantly, mutations that impair IP<sub>4</sub>/IP<sub>5</sub> production do specifically impair activation of this assembled complex, indicating a role for IP<sub>4</sub>/IP<sub>5</sub> production in transcriptional regulation. Genomic expression analysis in cells that fail to produce IP<sub>4</sub> or IP<sub>5</sub> indicates other targets for this newly appreciated paradigm of inositol phosphate-regulated gene expression.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3063197
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