title: The Expression of the Endogenous mTORC1 Inhibitor Sestrin 2 Is Induced by UVB and Balanced with the Expression Level of Sestrin 1.
abstract: Sestrin 2 (SESN2) is an evolutionarily conserved regulator of mechanistic target of rapamycin complex 1 (mTORC1) which controls central cellular processes such as protein translation and autophagy. Previous studies have suggested that SESN2 itself is subjected to regulation at multiple levels. Here, we investigated the expression of SESN2 in the skin and in isolated skin cells. SESN2 was detected by immunofluorescence analysis in fibroblasts and keratinocytes of human skin. Differentiation of epidermal keratinocytes was not associated with altered SESN2 expression and siRNA-mediated knockdown of SESN2 did not impair stratum corneum formation in vitro. However, SESN2 was increased in both cell types when the expression of its paralog SESN1 was blocked by siRNA-mediated knock down, indicating a compensatory mechanism for the control of expression. Irradiation with UVB but not with UVA significantly increased SESN2 expression in both keratinocytes and fibroblasts. Upregulation of SESN2 expression could be completely blocked by suppression of p53. These results suggest that SESN2 is dispensable for normal epidermal keratinization but involved in the UVB stress response of skin cells.
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Mlitz
authors.affiliation: Department of Biology and Women Beauty, Chanel R&T, Pantin, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Gendronneau
authors.affiliation: Department of Biology and Women Beauty, Chanel R&T, Pantin, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Berlin
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Buchberger
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
mesh_terms: D000328:Adult; D000368:Aged; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D055785:Gene Knockdown Techniques; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014466:Ultraviolet Rays; D055815:Young Adult; D000084622:Sestrins
chemical_list: D006360:Heat-Shock Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C117338:SESN1 protein, human; D000084622:Sestrins; C465398:SESN2 protein, human