Article

Regulation of Pluripotency and Cellular Reprogramming by the Ubiquitin-Proteasome System

Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Cell stem cell (Impact Factor: 22.15). 10/2012; 11(6). DOI: 10.1016/j.stem.2012.09.011
Source: PubMed

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.

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