title: Polyamine-modulated factor 1 binds to the human homologue of the 7a subunit of the Arabidopsis COP9 signalosome: implications in gene expression.
abstract: Polyamines have been identified to play a role in the transcription of various growth-related genes. The recently discovered polyamine responsive element and the associated trans-acting proteins involved in polyamine-regulated transcription have provided a model system for the study of the role of polyamines in transcription. Polyamine-modulated factor 1 (PMF-1) was identified as one of the transacting factors that binds to NF-E2 related factor-2 (Nrf-2) to regulate the transcription of spermidine/spermine N(1)-acetyltransferase (SSAT). The possibility that PMF-1 also binds to other proteins involved in transcriptional regulation cannot be ruled out. Using a yeast two-hybrid strategy, it was found that PMF-1 binds to a human homologue of the Arabidopsis COP9 signalosome subunit 7a (CSN 7) protein. In the present study, we describe human CSN 7, a 275-amino-acid- containing protein that may have a direct role in regulating gene expression. CSN 7 and PMF-1 bind to each other, as well as compete with each other for binding to Nrf-2. This competition for Nrf-2 binding and interaction with each other is implicated in the regulation of SSAT transcription. CSN 7 possesses a C-terminal coiled-coil domain similar to the domain that mediates the interaction between PMF-1 and Nrf-2, suggesting that coiled-coil domains also mediate the interaction between CSN 7 and PMF-1. Since CSN 7 does not contain a DNA-binding domain, its effects on transcription must occur in conjunction with binding to other proteins. The results presented here demonstrate that PMF-1 and Nrf-2 can act as protein partners of CSN 7.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Oncology Center, Bunting-Blaustein Cancer Research Building, Room 551, 1650 Orleans Street, Baltimore, MD 21231, U.S.A.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
authors.forename: Wendy
authors.initials: W
authors.lastname: Devereux
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Stewart
authors.forename: Robert A
authors.initials: RA
authors.lastname: Casero
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D000075686:COP9 Signalosome Complex; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010447:Peptide Hydrolases; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: C466088:COPS7A protein, human; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C120655:PMF1 protein, human; D021122:Protein Subunits; D011506:Proteins; D014157:Transcription Factors; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex