Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-beta signaling.

Experimental Cell Research
Reuben H KimMo K Kang

Abstract

We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-beta signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-beta signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-beta1 levels, phosphorylation of Smad2/3, and increased expression of p15(INK4B) and p57(KIP2). An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-beta1 induced dephosphorylation of Smad2/3, and diminished the level of p15(INK4B) and p57(KIP2). Moreover, Bmi-1 expression led to the inhibition of TGF-beta-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15(INK4B), and p57(KIP2). In addition, an exposure of senescent NHOK to TGF-beta receptor I kinase inhibitor or anti-TGF-beta antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inh...Continue Reading

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Citations

Mar 24, 2011·Journal of Dental Research·R H KimN-H Park
Jul 6, 2012·The Journal of Investigative Dermatology·Vladimir A BotchkarevMichael Y Fessing
Sep 17, 2011·Bioscience Reports·Kou-Juey Wu, Muh-Hwa Yang
Jan 9, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Da Hyun JangByung-Moo Min
Apr 1, 2017·PloS One·Min MinXiao-Yong Man
Dec 17, 2014·The Journal of Biological Chemistry·Manjari DimriGoberdhan P Dimri
Jul 15, 2017·Cellular and Molecular Life Sciences : CMLS·Corinne AbbadieAlbin Pourtier
Mar 5, 2015·The Journal of Biological Chemistry·Joon-Ho ChoGoberdhan P Dimri
Jul 4, 2015·Aging Cell·Reuben H KimNo-Hee Park
Jul 28, 2019·Oxidative Medicine and Cellular Longevity·Jingjing TaoQinghua Dong

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