title: Nonproteolytic roles of 19S ATPases in transcription of CIITApIV genes.
abstract: Accumulating evidence shows the 26S proteasome is involved in the regulation of gene expression. We and others have demonstrated that proteasome components bind to sites of gene transcription, regulate covalent modifications to histones, and are involved in the assembly of activator complexes in mammalian cells. The mechanisms by which the proteasome influences transcription remain unclear, although prior observations suggest both proteolytic and non-proteolytic activities. Here, we define novel, non-proteolytic, roles for each of the three 19S heterodimers, represented by the 19S ATPases Sug1, S7, and S6a, in mammalian gene expression using the inflammatory gene CIITApIV. These 19S ATPases are recruited to induced CIITApIV promoters and also associate with CIITA coding regions. Additionally, these ATPases interact with elongation factor PTEFb complex members CDK9 and Hexim-1 and with Ser5 phosphorylated RNA Pol II. Both the generation of transcripts from CIITApIV and efficient recruitment of RNA Pol II to CIITApIV are negatively impacted by siRNA mediated knockdown of these 19S ATPases. Together, these results define novel roles for 19S ATPases in mammalian gene expression and indicate roles for these ATPases in promoting transcription processes.
authors.affiliation: Graduate Program in Cell Biology and Immunology, Department of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Nagini
authors.initials: N
authors.lastname: Maganti
authors.affiliation: Graduate Program in Cell Biology and Immunology, Department of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Tomika D
authors.initials: TD
authors.lastname: Moody
authors.affiliation: Graduate Program in Cell Biology and Immunology, Department of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Agnieszka D
authors.initials: AD
authors.lastname: Truax
authors.affiliation: Graduate Program in Cell Biology and Immunology, Department of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Meghna
authors.initials: M
authors.lastname: Thakkar
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Spring
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Germann
authors.affiliation: Graduate Program in Cell Biology and Immunology, Department of Biology, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Susanna F
authors.initials: SF
authors.lastname: Greer
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000906:Antibodies / Q000737:chemistry; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D060588:LIM Domain Proteins / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry; D015534:Trans-Activators / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D006657:Histones; D060588:LIM Domain Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C092282:PSMC5 protein, human; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D012319:RNA Polymerase II; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities