title: Inhibition of Sp1 functions by its sequestration into PML nuclear bodies.
abstract: Promyelocytic leukemia nuclear bodies (PML NBs) are comprised of PML and a striking variety of its associated proteins. Various cellular functions have been attributed to PML NBs, including the regulation of gene expression. We report here that induced expression of PML recruits Sp1 into PML NBs, leading to the reduction of Sp1 transactivation function. Specifically, Chromatin immunoprecipitation (ChIP) assay demonstrated that induced expression of PML significantly diminishes the amount of Sp1 binding to its target gene promoter, immunofluorescence staining showed dramatic increase in the co-localization between PML and Sp1 upon induction of PML expression, moreover, PML and Sp1 co-fractionated in the core nuclear matrix. Our study further showed that PML promotes SUMOylation of Sp1 in a RING-motif-dependent manner, SUMOylation of Sp1 facilitates physical interaction between Sp1 and PML and recruitment of Sp1 into the PML NBs, the SUMO binding motif of PML was also important for its interaction with Sp1. The results of this study demonstrate a novel mechanism by which PML regulates gene expression through sequestration of the transcription factor into PML NBs.
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: June
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Zou
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Kun-Sang
authors.initials: KS
authors.lastname: Chang
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015530:Nuclear Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
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