Lipids and signal transduction in the nucleus.

Dygas, Anna; Barańska, Jolanta

doi:10.18388/abp.2001_3937

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…Mammalian CKs are thought to be cytoplasmic enzymes [1]. Yet, the nuclear localization of CKα, as observed in this study, supports the notion that the presence of CDP‐choline pathway enzymes, including CK in the nucleus, is required for the synthesis of endonuclear phosphatidylcholine, which, in turn, is an important source of diacylglycerol for nuclear lipid signaling [57–59].…”

Section: Discussionsupporting

confidence: 77%

Balance of human choline kinase isoforms is critical for cell cycle regulation

et al. 2012

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The enzyme choline kinase (CK), which catalyzes the phosphorylation of choline to phosphorylcholine in the presence of ATP, has an essential role in the biosynthesis of phosphatidylcholine, the major constituent of all mammalian cell membranes. CK is encoded by two separate genes expressing the three isoforms CKα1, CKα2 and CKβ that are active as homodimeric or heterodimeric species. Metabolic changes observed in various cancer cell lines and tumors have been associated with differential and marked up‐regulation of the CKα genes, and specific inhibition of CKα activity has been proposed as a potential anti‐cancer strategy. As a result, less attention has been given to CKβ and its interaction with CKα. With the aim of profiling the intracellular roles of CKα and CKβ, we used RNA interference (RNAi) as a molecular approach to down‐regulate the expression of CK in HeLa cells. Individual and simultaneous RNAi‐based silencing of the CK α and β isoforms was achieved using different combinations of knockdown strategies. Efficient knockdown was confirmed by immunodetection using our isoform‐specific antibodies and by quantitative real‐time PCR. Our analyses of the phenotypic consequences of CK depletion showed the expected lethal effect of CKα knockdown. However, CKβ‐ and CKα + CKβ‐silenced cells had no aberrant phenotype. Therefore, our results support the hypothesis that the balance of the α and β isoforms is critical for cancer cell survival. The suppression of the cancer cell killing effect of CKα silencing by simultaneous knockdown of both isoforms implies that a more effective CK‐based anti‐cancer strategy can be achieved by reducing cross‐reactivity with CKβ.

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Section: Discussionsupporting

confidence: 77%

Balance of human choline kinase isoforms is critical for cell cycle regulation

et al. 2012

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“…The differential activation and subcellular translocation of specific PKC isoenzymes could be thus linked to the generation of endogenous PKC activators in specific subcellular compartments. In the nucleus, activation of phospholipase Cb results in the generation of 1,2-diacylglycerol (DAG), an activator of PKC (Nishizuka, 1995;D'Santos et al, 1998;Martelli et al, 1999;Chi & Crabtree, 2000;Dygas & Barañska, 2001). All conventional isoforms of PKC (a, b and g) that have been detected in the nucleus are Ca 2+ , DAG and PS dependent (Martelli et al, 1999;.…”

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confidence: 99%

Ca2+-dependent phosphatidylserine synthesis in immature and mature starfish oocytes.

Dygas¹,

Barańska²,

Santella³

2003

Acta Biochim Pol

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We found that in starfish oocytes two different enzymes, phosphatidylserine synthase-1 (PSS1) and -2 (PSS2), which synthesize phosphatidylserine by a base-exchange reaction, are present. We studied phosphatidylserine synthesis in immature oocytes which still contain the nucleus (germinal vesicles) and in mature cells, in which the re-initiation of the meiotic cycle induced by the hormone 1-methyladenine led to structural changes in the endoplasmic reticulum, to the disappearance of the nuclear envelope and to the intermixing of the nucleoplasm with the cytoplasm. It was found that the levels of PSS1 and PSS2 transcripts were higher in immature and mature oocytes, respectively. The level of the expressed PSS2 protein, higher than that of PSS1, was not influenced by the maturation process, whereas the level of PSS1 protein was higher in immature than in mature oocytes. Serine incorporation into phosphatidylserine was enhanced in immature oocytes. The depletion of calcium stores by thapsigargin resulted in 50% lowering of phosphatidylserine synthesis. We suggest that changes in phosphatidylserine synthesis may be affected by the release of calcium stored in the nuclear envelope and in the endoplasmic reticulum, the membranes that undergo disintegration and fragmentation during meiosis. The reason for the greater synthesis of PS may be the higher level of expression of PSS1 in immature oocytes.

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“New”‐clear functions of PDK1: Beyond a master kinase?

Kikani

Dong

Liu

2005

J of Cellular Biochemistry

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Activation of cytosolic phosphoinositide-3 kinase (PI-3K) signaling pathway has been well established to regulate gene expression, cell cycle, and survival by feeding signals to the nucleus. In addition, strong evidences accumulated over the past few years indicate the presence of an autonomous inositol lipid metabolism and PI-3K signaling within the nucleus. Much less, however, is known about the role and regulation of this nuclear PI-3K pathway. Components of the PI-3K signaling pathway, including PI 3-kinase and its downstream kinase Akt, have been identified at the nuclear level. Consistent with the presence of a complete PI-3K signaling pathway in the nucleus, we have recently found that phosphoinositide-dependent kinase 1 (PDK1), a kinase functioning downstream of PI-3K and upstream of Akt, is a nucleo-cytoplasmic shuttling protein. In the present review, we update our current knowledge on the regulatory mechanisms and the functional roles of PDK1 nuclear translocation. We also summarize some of the kinase-independent activities of PDK1 in cell signaling.

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Lipids and signal transduction in the nucleus.

Cited by 4 publications

References 48 publications

Balance of human choline kinase isoforms is critical for cell cycle regulation

Balance of human choline kinase isoforms is critical for cell cycle regulation

Ca2+-dependent phosphatidylserine synthesis in immature and mature starfish oocytes.

“New”‐clear functions of PDK1: Beyond a master kinase?

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