title: NAC1, a POZ/BTB protein that functions as a corepressor.
abstract: We now demonstrate that NAC1 acts as a corepressor for other POZ/BTB proteins. NAC1 is a POZ/BTB motif containing transcriptional repressor protein. In a mammalian two hybrid assay in neuronal (N2A) cells and non-neuronal (HEK 293T) cells, VP16 activation domain tagged NAC1 resulted in significant reversal of transcriptional inhibition with the Gal4-ZID, Gal4-BCL6, Gal4-ZF5, and kelch proteins Gal4-MAYVEN and Gal4-NRP/B fusion proteins. We also observed similar results with another corepressor, BCoR Gal4 fusion protein. NAC1 potentiated ZF5 mediated repression in Gal4-DBD fusion transient assays. GST pulldown assays further confirmed protein-protein interactions between these proteins and NAC1. Both the NAC1 isoforms demonstrated selective interaction through the POZ/BTB domain but not with the non-POZ/BTB region. Endogenous NAC1 and BCL6 physically associated in CNS regions. Strikingly, NAC1 did not interact with the pro-myelocytic leukemia zinc finger protein (PLZF), another POZ/BTB protein that is not found in the adult brain. Therefore, we conclude that NAC1 functions as a corepressor for POZ/BTB proteins expressed in the mature CNS.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: Laxminarayana
authors.initials: L
authors.lastname: Korutla
authors.forename: Peijie
authors.initials: P
authors.lastname: Wang
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Jackson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Mackler
mesh_terms: D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: C411984:BCOR protein, human; D051741:Kruppel-Like Transcription Factors; C516477:NACC1 protein, human; C484605:Nacc1 protein, mouse; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C092037:ZBTB16 protein, human