Редактирование: DIRAS3 (раздел)

==Publications==

{{medline-entry
|title=Silencing of the small GTPase [[DIRAS3]] induces cellular senescence in human white adipose stromal/progenitor cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28316325
|abstract=Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 ([[DIRAS3]]), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that [[DIRAS3]] knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. [[DIRAS3]] KD ASCs lose the potential to form colonies and are negative for Ki-67. Moreover, silencing of [[DIRAS3]] results in a premature senescence phenotype. This is characterized by senescence-associated [i]β[/i]-galactosidase positive enlarged ASCs containing increased p16  level and activated retinoblastoma protein. [[DIRAS3]] KD ASCs form senescence-associated heterochromatic foci as shown by increased level of γ-H2A.X positive foci. Furthermore, these cells express a senescence-associated secretory phenotype characterized by increased interleukin-8 secretion. Human [[DIRAS3]] KD ASCs develop also a senescence phenotype in sWAT of SCID mice. Finally, we show that [[DIRAS3]] KD in ASCs stimulates both adipogenic differentiation and premature senescence. In conclusion, our data suggest that silencing of [[DIRAS3]] in ASCs and subsequently hyper-activation of Akt-mTOR drives adipogenesis and premature senescence. Moreover, differentiating ASCs and/or mature adipocytes may acquire features of cellular senescence.
|mesh-terms=* Adipocytes
* Adipogenesis
* Adipose Tissue, White
* Cell Proliferation
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p16
* Female
* Gene Silencing
* Humans
* Proto-Oncogene Proteins c-akt
* Signal Transduction
* Stem Cells
* TOR Serine-Threonine Kinases
* beta-Galactosidase
* rho GTP-Binding Proteins
|keywords=* DIRAS3
* adipocyte
* adipogenesis
* adipose stem cell
* adipose stromal/progenitor cell
* aging
* mTOR
* obesity
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391236
}}
{{medline-entry
|title=Weight Loss Upregulates the Small GTPase [[DIRAS3]] in Human White Adipose Progenitor Cells, Which Negatively Regulates Adipogenesis and Activates Autophagy via Akt-mTOR Inhibition.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27211557
|abstract=Long-term weight-loss (WL) interventions reduce insulin serum levels, protect from obesity, and postpone age-associated diseases. The impact of long-term WL on adipose-derived stromal/progenitor cells (ASCs) is unknown. We identified [[DIRAS3]] and IGF-1 as long-term WL target genes up-regulated in ASCs in subcutaneous white adipose tissue of formerly obese donors (WLDs). We show that [[DIRAS3]] negatively regulates Akt, mTOR and ERK1/2 signaling in ASCs undergoing adipogenesis and acts as a negative regulator of this pathway and an activator of autophagy. Studying the IGF-1-[[DIRAS3]] interaction in ASCs of WLDs, we demonstrate that IGF-1, although strongly up-regulated in these cells, hardly activates Akt, while ERK1/2 and S6K1 phosphorylation is activated by IGF-1. Overexpression of [[DIRAS3]] in WLD ASCs completely inhibits Akt phosphorylation also in the presence of IGF-1. Phosphorylation of ERK1/2 and S6K1 is lesser reduced under these conditions. In conclusion, our key findings are that [[DIRAS3]] down-regulates Akt-mTOR signaling in ASCs of WLDs. Moreover, [[DIRAS3]] inhibits adipogenesis and activates autophagy in these cells. 
|mesh-terms=* Adipogenesis
* Adult
* Animals
* Autophagy
* Cell Differentiation
* Cells, Cultured
* Female
* Gene Expression Regulation
* Humans
* Insulin-Like Growth Factor I
* MAP Kinase Signaling System
* Mice
* Middle Aged
* Phosphorylation
* Proto-Oncogene Proteins c-akt
* Stem Cells
* Subcutaneous Fat
* TOR Serine-Threonine Kinases
* Weight Loss
* Young Adult
* rho GTP-Binding Proteins
|keywords=* Adipogenesis
* Aging
* Akt
* Autophagy
* Caloric restriction
* DIRAS3
* ERK1/2
* Human adipose-derived stromal/progenitor cells
* IGF-1
* Insulin
* Obesity
* Weight loss
* mTOR
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856797
}}
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