Nuclear Phosphoinositides—Versatile Regulators of Genome Functions

Castaño, Enrique; Yıldırım, Serkan; Fáberová, Veronika; Krausová, Alžběta; Ulicna, Livia; Paprčková, Darina; Sztacho, Martin; Hozák, Pavel

doi:10.3390/cells8070649

Cited by 27 publications

(43 citation statements)

References 145 publications

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“…Until now, a plethora of studies have confirmed the existence of PIs and their metabolizing enzymes, i.e., lipases, kinases, and phosphatases, in several subnuclear compartments. This generates a distinct PI pool capable of regulating several essential nuclear processes, such as chromatin remodeling, DNA repair, RNA processing, and gene transcription [1,26,37]. The ability of PI metabolizing enzymes to localize within the same nuclear subcompartments as their respective substrate PI or product confirms their direct involvement in nuclear PI metabolism ( Figure 2).…”

Section: Nuclear Structure and Nuclear Inositidesmentioning

confidence: 81%

“…Nuclear PtdIns5P regulates chromatin remodeling by interacting with the histone code reader associated with the chromatin complex ING2 (inhibitor of growth protein 2), which is a subunit of the HDAC1 complex (Sin3a-histone deacetylase 1). In particular, PtdIns5P modulates the binding of ING2 to chromatin and also participates in epigenetic gene expression and DNA damage [37,74].…”

Section: Chromatin Remodelingmentioning

confidence: 99%

“…PtdIns(3,4,5)P3 is involved in major signaling axes implicated in cell survival by promoting the expression of anti-apoptotic signals [37]. At the nuclear level, PtdIns(3,4,5)P3 is stimulated by NGF (nerve growth factor) to mediate cell survival.…”

Section: Cell Survivalmentioning

confidence: 99%

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Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes

Xian

Obeng

Ratti

et al. 2020

Cells

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Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by peripheral blood cytopenia and abnormal myeloproliferation, as well as a variable risk of evolution into acute myeloid leukemia (AML). The nucleus is a highly organized organelle with several distinct domains where nuclear inositides localize to mediate essential cellular events. Nuclear inositides play a critical role in the modulation of erythropoiesis or myelopoiesis. Here, we briefly review the nuclear structure, the localization of inositides and their metabolic enzymes in subnuclear compartments, and the molecular aspects of nuclear inositides in MDS.

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Section: Nuclear Structure and Nuclear Inositidesmentioning

confidence: 81%

Section: Chromatin Remodelingmentioning

confidence: 99%

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Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes

Xian

Obeng

Ratti

et al. 2020

Cells

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“…Nuclear PIs are critical signal molecules in several nuclear mechanisms such as DNA transcription, pre-mRNA processing or RNA export (Blind et al, 2012;Castano et al, 2019). PI(4,5)P2, labeled by an IgM antibody (2C11), has been found in the nucleus in nonmembrane compartments, nuclear speckles, nucleoli and nuclear lipid islets recently involved in RNA polymerase II transcription (Sobol et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…A series of reports have indicated the presence of PI(4,5)P2 in the nucleus (Osborne et al, 2001), particularly in speckles and in nuclear lipid islets (Castano et al, 2019). Nuclear PI(4,5)P2 could be further phosphorylated through the action of inositol phosphate multikinase (IPMK) to produce nuclear PI(3,4,5)P3 (Resnick et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update

Ramos

Ghosh

Suhel

et al. 2020

Advances in Biological Regulation

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Phosphoinositides (PIs) are phosphorylated derivatives of phosphatidylinositol. They act as signaling molecules linked to essential cellular mechanisms in eukaryotic cells, such as cytoskeleton organization, mitosis, polarity, migration or invasion. PIs are phosphorylated and dephosphorylated by a large number of PI kinases and PI phosphatases acting at the 5-, 4-and 3position of the inositol ring. PI 5-phosphatases i.e. OCRL, INPP5B, SHIP1/2, Synaptojanin 1/2, INPP5E, INPP5J, SKIP (INPP5K) are enzymes that dephosphorylate the 5-phosphate position of PIs. Several human genetic diseases such as the Lowe syndrome, some congenital muscular dystrophy and opsismodysplasia are due to mutations in PI phosphatases, resulting in loss-offunction. The PI phosphatases are also up or down regulated in several human cancers such as glioblastoma or breast cancer. Their cellular localization, that is dynamic and varies in response to stimuli, is an important issue to understand function. This is the case for two members of the PI 5-phosphatase SKIP and SHIP2. Both enzymes are in ruffles, plasma membranes, the endoplasmic reticulum, a situation that is unique for SKIP, and the nucleus. Following localization, PI 5phosphatases act on specific cellular pools of PIs, which in turn interact with target proteins. Nuclear PIs have emerged as regulators of genome functions in different area of cell signaling. They often localize to nuclear speckles, as do several PI metabolizing kinases and phosphatases. We asked whether SKIP and SHIP2 could have an impact on nuclear PI(4,5)P2. In two glioblastoma cell models, lowering SKIP expression had an impact on nuclear PI(4,5)P2. In a model of SHIP2 deletion in MCF-7 cells, no change in nuclear PI(4,5)P2 was observed. Finally, we present evidence of an anti-tumoral role of SKIP in vivo, in xenografts using as model U87shSKIP cells.

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Viruses and phospholipids: Friends and foes during infection

Rattay

Hufbauer

Hoboth

et al. 2023

Journal of Medical Virology

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Viruses have evolved complex and dynamic interactions with their host cells to enable viral replication. In recent years, insights have been gained into the increasingly important role of the host cell lipidome in the life cycle of several viruses. In particular, viruses target phospholipid signaling, synthesis, and metabolism to remodel their host cells into an optimal environment for their replication cycle. Conversely, phospholipids and their associated regulatory enzymes can interfere with viral infection or replication. This review highlights examples of different viruses that illustrate the importance of these diverse virus–phospholipid interactions in different cellular compartments, particularly the role of nuclear phospholipids and their association with human papillomavirus (HPV)‐mediated cancer development.

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Nuclear Phosphoinositides—Versatile Regulators of Genome Functions

Cited by 27 publications

References 145 publications

Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes

Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes

Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update

Viruses and phospholipids: Friends and foes during infection

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