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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line
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Central Nervous System / metabolism*
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Genes, Reporter / genetics
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Humans
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / metabolism
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Mice
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Promyelocytic Leukemia Zinc Finger Protein
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary / genetics
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism*
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Transcription, Genetic / genetics*
Substances
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BCOR protein, human
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Kruppel-Like Transcription Factors
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NACC1 protein, human
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Nacc1 protein, mouse
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Neoplasm Proteins
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Nerve Tissue Proteins
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Promyelocytic Leukemia Zinc Finger Protein
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Protein Isoforms
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Repressor Proteins
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ZBTB16 protein, human