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Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling.

Jerde TJ - J Signal Transduct (2015)

Bottom Line: In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells.Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling.The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, IU-Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.

ABSTRACT
Phosphatase and tensin homologue (PTEN) is a critical cell endogenous inhibitor of phosphoinositide signaling in mammalian cells. PTEN dephosphorylates phosphoinositide trisphosphate (PIP3), and by so doing PTEN has the function of negative regulation of Akt, thereby inhibiting this key intracellular signal transduction pathway. In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells. Numerous reports exist regarding mutations in PTEN leading to unregulated Akt and human disease, most notably cancer. However, less is commonly known about nonmutational regulation of PTEN. This review focuses on an emerging literature on the regulation of PTEN at the transcriptional, posttranscriptional, translational, and posttranslational levels. Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling. The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival. Perturbations of PTEN regulation consequently lead to human diseases such as cancer, chronic inflammatory syndromes, developmental abnormalities, diabetes, and neurodegeneration.

No MeSH data available.


Related in: MedlinePlus

Precise regulation of PTEN expression, activity, or localization has profound effects on the development of numerous organ systems. Disruption of PTEN at the level of transcription, mRNA stability, protein stability, enzymatic function, or cellular location results in disruption of these developmental systems.
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fig2: Precise regulation of PTEN expression, activity, or localization has profound effects on the development of numerous organ systems. Disruption of PTEN at the level of transcription, mRNA stability, protein stability, enzymatic function, or cellular location results in disruption of these developmental systems.

Mentions: At an organismal level, PTEN plays several critical roles in the early control of the patterning of embryos. First, PTEN regulation of cell migration is known to control specification of the anterior-posterior axis of mouse embryos [20]. Embryos that lack PTEN expression exhibit a notable set of morphological defects including the failure to correctly specify the anterior-posterior body axis, improper separation of body foci, and decreased coordinated migration of cells along the body axis. PTEN is also necessary for gastrulation of embryos. PTEN is highly expressed from the midblastula transition through completion of gastrulation and embryonic layer separation [21]. In this process, PTEN coordinates cell cycle elongation and cellular morphogenesis. Embryos lacking PTEN fail to exhibit proper patterning from the blastula into the germ layers. Lethality of these embryos soon follows. At the postgastrulation stage, PTEN localization can be found throughout ectodermal, endodermal, and mesodermal-derived tissue, including the developmental precursors of the central nervous system and skin, the liver and gastrointestinal tract, the urogenital sinus, heart, and skeletal muscle [19, 20]. Anatomy of PTEN systems effects highlighed in Figure 2. Following the separation of the germ layers, PTEN exerts dynamic roles throughout development, across numerous organ systems. The following highlights recent findings.


Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling.

Jerde TJ - J Signal Transduct (2015)

Precise regulation of PTEN expression, activity, or localization has profound effects on the development of numerous organ systems. Disruption of PTEN at the level of transcription, mRNA stability, protein stability, enzymatic function, or cellular location results in disruption of these developmental systems.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539077&req=5

fig2: Precise regulation of PTEN expression, activity, or localization has profound effects on the development of numerous organ systems. Disruption of PTEN at the level of transcription, mRNA stability, protein stability, enzymatic function, or cellular location results in disruption of these developmental systems.
Mentions: At an organismal level, PTEN plays several critical roles in the early control of the patterning of embryos. First, PTEN regulation of cell migration is known to control specification of the anterior-posterior axis of mouse embryos [20]. Embryos that lack PTEN expression exhibit a notable set of morphological defects including the failure to correctly specify the anterior-posterior body axis, improper separation of body foci, and decreased coordinated migration of cells along the body axis. PTEN is also necessary for gastrulation of embryos. PTEN is highly expressed from the midblastula transition through completion of gastrulation and embryonic layer separation [21]. In this process, PTEN coordinates cell cycle elongation and cellular morphogenesis. Embryos lacking PTEN fail to exhibit proper patterning from the blastula into the germ layers. Lethality of these embryos soon follows. At the postgastrulation stage, PTEN localization can be found throughout ectodermal, endodermal, and mesodermal-derived tissue, including the developmental precursors of the central nervous system and skin, the liver and gastrointestinal tract, the urogenital sinus, heart, and skeletal muscle [19, 20]. Anatomy of PTEN systems effects highlighed in Figure 2. Following the separation of the germ layers, PTEN exerts dynamic roles throughout development, across numerous organ systems. The following highlights recent findings.

Bottom Line: In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells.Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling.The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, IU-Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.

ABSTRACT
Phosphatase and tensin homologue (PTEN) is a critical cell endogenous inhibitor of phosphoinositide signaling in mammalian cells. PTEN dephosphorylates phosphoinositide trisphosphate (PIP3), and by so doing PTEN has the function of negative regulation of Akt, thereby inhibiting this key intracellular signal transduction pathway. In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells. Numerous reports exist regarding mutations in PTEN leading to unregulated Akt and human disease, most notably cancer. However, less is commonly known about nonmutational regulation of PTEN. This review focuses on an emerging literature on the regulation of PTEN at the transcriptional, posttranscriptional, translational, and posttranslational levels. Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling. The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival. Perturbations of PTEN regulation consequently lead to human diseases such as cancer, chronic inflammatory syndromes, developmental abnormalities, diabetes, and neurodegeneration.

No MeSH data available.


Related in: MedlinePlus