Nanog induces suppression of senescence through downregulation of p27KIP1 expression

Journal of Cell Science
Bernhard MünstFrank Edenhofer

Abstract

A comprehensive analysis of the molecular network of cellular factors establishing and maintaining pluripotency as well as self renewal of pluripotent stem cells is key for further progress in understanding basic stem cell biology. Nanog is necessary for the natural induction of pluripotency in early mammalian development but dispensable for both its maintenance and its artificial induction. To gain further insight into the molecular activity of Nanog, we analyzed the outcomes of Nanog gain-of-function in various cell models employing a recently developed biologically active recombinant cell-permeant protein, Nanog-TAT. We found that Nanog enhances the proliferation of both NIH 3T3 and primary fibroblast cells. Nanog transduction into primary fibroblasts results in suppression of senescence-associated β-galactosidase activity. Investigation of cell cycle factors revealed that transient activation of Nanog correlates with consistent downregulation of the cell cycle inhibitor p27(KIP1) (also known as CDKN1B). By performing chromatin immunoprecipitation analysis, we confirmed bona fide Nanog-binding sites upstream of the p27(KIP1) gene, establishing a direct link between physical occupancy and functional regulation. Our data demon...Continue Reading

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Citations

Jul 24, 2018·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Mei-Yin YeYuh-Ling Chen
Aug 19, 2020·Molecular Biotechnology·Krishna Kumar HaridhasapavalanRajkumar P Thummer
Dec 15, 2020·Protein Expression and Purification·Gloria NarayanRajkumar P Thummer
Feb 10, 2021·Bioprocess and Biosystems Engineering·Krishna Kumar HaridhasapavalanRajkumar P Thummer
Mar 3, 2021·Applied Microbiology and Biotechnology·Krishna Kumar HaridhasapavalanRajkumar P Thummer
Apr 23, 2021·Cellular and Molecular Life Sciences : CMLS·Menno Ter Huurne, Hendrik G Stunnenberg
May 1, 2021·3 Biotech·Chandrima DeyRajkumar P Thummer

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Methods Mentioned

BETA
immunoprecipitation
PCR
ChIP
FCS
dot blot

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