Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system

Shannon M. Buckley, Beatriz Aranda-Orgilles, Alexandros Strikoudis, Effie Apostolou, Evangelia Loizou, Kelly Moran-Crusio, Charles L. Farnsworth, Antonius A. Koller, Ramanuj Dasgupta, Jeffrey C. Silva, Matthias Stadtfeld, Konrad Hochedlinger, Emily I. Chen, Iannis Aifantis

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Although transcriptional regulation of stem cell pluripotency and differentiation has been extensively studied, only a small number of studies have addressed the roles for posttranslational modifications in these processes. A key mechanism of posttranslational modification is ubiquitination by the ubiquitin-proteasome system (UPS). Here, using shotgun proteomics, we map the ubiquitinated protein landscape during embryonic stem cell (ESC) differentiation and induced pluripotency. Moreover, using UPS-targeted RNAi screens, we identify additional regulators of pluripotency and differentiation. We focus on two of these proteins, the deubiquitinating enzyme Psmd14 and the E3 ligase Fbxw7, and characterize their importance in ESC pluripotency and cellular reprogramming. This global characterization of the UPS as a key regulator of stem cell pluripotency opens the way for future studies that focus on specific UPS enzymes or ubiquitinated substrates.

Original languageEnglish (US)
Pages (from-to)783-798
Number of pages16
JournalCell Stem Cell
Volume11
Issue number6
DOIs
StatePublished - Dec 7 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Buckley, S. M., Aranda-Orgilles, B., Strikoudis, A., Apostolou, E., Loizou, E., Moran-Crusio, K., Farnsworth, C. L., Koller, A. A., Dasgupta, R., Silva, J. C., Stadtfeld, M., Hochedlinger, K., Chen, E. I., & Aifantis, I. (2012). Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system. Cell Stem Cell, 11(6), 783-798. https://doi.org/10.1016/j.stem.2012.09.011