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

Neurochem Int. 2009 Mar-Apr;54(3-4):245-52. doi: 10.1016/j.neuint.2008.12.008. Epub 2008 Dec 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Central Nervous System / metabolism*
  • Genes, Reporter / genetics
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Promyelocytic Leukemia Zinc Finger Protein
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Transcription, Genetic / genetics*

Substances

  • BCOR protein, human
  • Kruppel-Like Transcription Factors
  • NACC1 protein, human
  • Nacc1 protein, mouse
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Promyelocytic Leukemia Zinc Finger Protein
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • ZBTB16 protein, human