title: Reversible acetylation of Lin28 mediated by PCAF and SIRT1.
abstract: Lin28 is a small RNA-binding protein that plays an important role in regulating developmental timing, stem cell reprogramming, and oncogenesis. However, the significance of the effect of post-translational modifications on Lin28 activity is not fully understood. In this study, we demonstrated that PCAF directly interacted with and acetylated Lin28. We also showed that the acetylation of Lin28 can be specifically reversed by the deacetylase SIRT1. These findings suggest that the PCAF/SIRT1 balance plays an important role in regulating Lin28 activity. Furthermore, we found that the cold shock domain of Lin28 is the major target of PCAF-mediated acetylation, which leads to a severe reduction in the Lin28 protein levels and an increase in the level of mature let-7a. This study provides the first demonstration that post-translational modification regulates Lin28 activity during let-7a biogenesis and sheds light on the regulation of Lin28 in ES cells and carcinogenesis.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Ling-xia
authors.initials: LX
authors.lastname: Wang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Qu
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address: yezhang@ibms.pumc.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address: yfshen@imicams.ac.cn.
authors.forename: Yu-fei
authors.initials: YF
authors.lastname: Shen
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D008156:Luciferases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D056564:Sirtuin 1; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000715187:Lin28A protein, human; C447939:SIRT1 protein, human
keywords: Acetylation; Lin28; PCAF; Protein stability; SIRT1