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NAC1, a POZ/BTB protein that functions as a corepressor.

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.

Pubmed ID: 19121354

Authors

  • Korutla L
  • Wang P
  • Jackson TG
  • Mackler SA

Journal

Neurochemistry international

Publication Data

March 6, 2009

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA 11809-03

Mesh Terms

  • Animals
  • Cell Line
  • Central Nervous System
  • Genes, Reporter
  • Humans
  • Kruppel-Like Transcription Factors
  • Mice
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription, Genetic