A novel gene expression pathway regulated by nuclear phosphoinositides

Mellman, David L.; Anderson, Richard A.

doi:10.1016/j.advenzreg.2009.01.007

Cited by 20 publications

(18 citation statements)

References 146 publications

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“…A noncanonical poly(A) polymerase, named Star-PAP, has been identified as a protein that interacts with PIPKI␣ in nuclear speckles (1029). This protein adds poly(A) tails to a selected group of mRNAs, and its activity is highly stimulated by PtdIns(4,5)P 2 (1028,1029). Curiously, a low activity form of a DNA polymerase was also shown to be activated by PtdIns4P or its hydrolytic product, Ins(1,4)P 2 (1507,1508).…”

Section: Nucleusmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,396

1,655

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Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

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Section: Nucleusmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,396

1,655

View full text Add to dashboard Cite

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“…The Star-PAP complex represents a site where multiple phosphoinositide-signaling pathways converge to control the synthesis of selected mRNAs (Mellman and Anderson, 2009).…”

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confidence: 99%

The physiology and pathology of inositide signaling in the nucleus

Ramazzotti

Faenza

Fiume

et al. 2010

Journal Cellular Physiology

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“…This finding suggests that these kinases are involved in gene expression. Although some attempts have been made to elucidate the regulation of gene expression by these nuclear phosphoinositides (Mellman et al, 2008;Mellman and Anderson, 2009;Keune et al, 2011), the mechanism by which they directly regulate these functions remains unknown. Recently, Wenning et al (2009) have suggested that PIPKIIα may be involved in the regulation of b-globin gene expression in α-thalassemia patients; however, none of the studies in the literature to date have investigated the normal profiles of PIPKs in erythroid cells from healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

“…PIPKI and PIPKII have 3 isoforms (a, β, and g) and produce PI4,5P 2 by catalyzing the phosphorylation of phosphatidylinositol-4-phosphate and phosphatidylinositol-5-phosphate, respectively (Hinchliffe and Irvine, 2006;Wilcox And Hinchliffe, 2008;Mellman and Anderson, 2009). PIPKIs are found in the plasma membrane, focal adhesions, Golgi, and nucleus, and their activities appear to be necessary in endocytosis, adhesion, secretion, and actin rearrangements.…”

Section: Introductionmentioning

confidence: 99%

Expression profiles of phosphatidylinositol phosphate kinase genes during normal human in vitro erythropoiesis

Zaccariotto¹,

Lanaro²,

Albuquerque³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Phosphatidylinositol phosphate kinases (PIPKs) are enzymes that participate in diverse intracellular signaling pathways. They are classified into 3 functionally distinct subfamilies -PIPKI (a, b, g), PIPKII (a, b, g), and PIPKIII -located in various subcellular compartments. Recently, the PIPKIIa and b-globin genes were found to be overexpressed in reticulocytes from 2 siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIa and the production of globins. The main aim of this study was to determine the expression profiles of PIPK genes in healthy individuals during in vitro erythropoiesis using quantitative real-time polymerase chain reaction and to compare these profiles with profiles of globin genes. Our results showed that expression of all PIPKs increases as the cells differentiate, coinciding with the expression profiles of globins. Analysis of the effects of globins on PIPK genes revealed that they varied significantly between the globins, the most noticeable being the effect of a-globin on PIPKIIa (P < 0.0001) and g-globin on PIPKIIg (P < 0.0001). The relationship between the expression of PIPKs and globin genes was statistically significant, particularly between PIPKIIa and a-globin (P = 0.0002) and PIPKIIg and b-globin (P < 0.0001). Linear correlation analysis revealed a strong relationship between PIPKIIa and a-globin genes. This study is the first to establish the expression profiles of PIPK genes during in vitro erythropoiesis in healthy individuals and suggests a parallel between the expression of PIPK and globin genes, reinforcing the hypothesis that they may be related.

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A novel gene expression pathway regulated by nuclear phosphoinositides

Cited by 20 publications

References 146 publications

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

The physiology and pathology of inositide signaling in the nucleus

Expression profiles of phosphatidylinositol phosphate kinase genes during normal human in vitro erythropoiesis

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