TY - JOUR
T1 - Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system
AU - Buckley, Shannon M.
AU - Aranda-Orgilles, Beatriz
AU - Strikoudis, Alexandros
AU - Apostolou, Effie
AU - Loizou, Evangelia
AU - Moran-Crusio, Kelly
AU - Farnsworth, Charles L.
AU - Koller, Antonius A.
AU - Dasgupta, Ramanuj
AU - Silva, Jeffrey C.
AU - Stadtfeld, Matthias
AU - Hochedlinger, Konrad
AU - Chen, Emily I.
AU - Aifantis, Iannis
N1 - Funding Information:
We would like to thank Dr. I. Lemischka for the Nanog-GFP reporter ESC line; Dr. S. Dalton for the c-myc T58A ER ESCs; Drs. D. Reinberg, R. Bonasio, and L.-A. Rojas for providing the pINTA-SF vectors; Drs. F. Gonsalves and Beatrix Ueberheide for helpful discussions; and Drs. H. Li and T. Liu at the Center for Advanced Proteomics Research, New Jersey School of Medicine, for selected mass-spectrometry analysis. We would also like to thank the NYU Genome Technology Center (supported in part by National Institutes of Health [NIH]/National Cancer Institute [NCI] grant P30 CA016087-30) for expert assistance with microarray experiments. I.A. is supported by the NIH (RO1CA133379, RO1CA105129, RO1CA149655, and RO1GM088847) and the NYSTEM program of the New York State Health Department. E.I.C. is supported by the NIH (1U19A1091175-01 and 1S10 RR023680-1). S.M.B. is supported by the NYU Hematology/Oncology NIH training grant (5T32HL007151-33) and the NIH institutional training grant (1T32CA160002-01), B.A.-O. is supported by the Alexander von Humboldt Foundation, and A.S. is supported by NYSTEM institutional NYU Stem Cell training grant (C026880). I.A. and K.H. are Howard Hughes Medical Institute Early Career Scientists.
PY - 2012/12/7
Y1 - 2012/12/7
N2 - 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.
AB - 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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U2 - 10.1016/j.stem.2012.09.011
DO - 10.1016/j.stem.2012.09.011
M3 - Article
C2 - 23103054
AN - SCOPUS:84870945375
SN - 1934-5909
VL - 11
SP - 783
EP - 798
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 6
ER -