| Structural highlights
Function
NACC1_HUMAN Functions as a transcriptional repressor. Seems to function as a transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell proliferation and survival. This may be mediated at least in part through repressing transcriptional activity of GADD45GIP1. Required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines.[1] [2]
Publication Abstract from PubMed
Nucleus accumbens-associated protein 1 (NAC1) is a nuclear protein that harbors an amino-terminal BTB domain and a carboxyl-terminal BEN domain. NAC1 appears to play significant and diverse functions in cancer and stem cell biology. Here we demonstrated that the BEN domain of NAC1 is a sequence-specific DNA-binding domain. We selected the palindromic 6 bp motif ACATGT as a target sequence by using a PCR-assisted random oligonucleotide selection approach. The interaction between NAC1 and target DNA was characterized by gel shift assays, pull-down assays, isothermal titration calorimetry (ITC), chromatin-immunoprecipitation assays, and NMR chemical shifts perturbation (CSP). The solution NMR structure revealed that the BEN domain of human NAC-1 is composed of five conserved alpha helices and two short beta sheets, with an additional hitherto unknown N-terminal alpha helix. In particular, ITC clarified that there are two sequential events in the titration of the BEN domain of NAC1 into the target DNA. The ITC results were further supported by CSP data and structure analyses. Furthermore, live cell photobleaching analyses revealed that the BEN domain of NAC1 alone was unable to interact with chromatin/other proteins in cells.
Nucleus Accumbens-Associated Protein 1 Binds DNA Directly through the BEN Domain in a Sequence-Specific Manner.,Nakayama N, Sakashita G, Nagata T, Kobayashi N, Yoshida H, Park SY, Nariai Y, Kato H, Obayashi E, Nakayama K, Kyo S, Urano T Biomedicines. 2020 Dec 14;8(12). pii: biomedicines8120608. doi:, 10.3390/biomedicines8120608. PMID:33327466[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nakayama K, Nakayama N, Davidson B, Sheu JJ, Jinawath N, Santillan A, Salani R, Bristow RE, Morin PJ, Kurman RJ, Wang TL, Shih IeM. A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18739-44. Epub 2006 Nov 27. PMID:17130457 doi:http://dx.doi.org/0604083103
- ↑ Nakayama K, Nakayama N, Wang TL, Shih IeM. NAC-1 controls cell growth and survival by repressing transcription of Gadd45GIP1, a candidate tumor suppressor. Cancer Res. 2007 Sep 1;67(17):8058-64. PMID:17804717 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-1357
- ↑ Nakayama N, Sakashita G, Nagata T, Kobayashi N, Yoshida H, Park SY, Nariai Y, Kato H, Obayashi E, Nakayama K, Kyo S, Urano T. Nucleus Accumbens-Associated Protein 1 Binds DNA Directly through the BEN Domain in a Sequence-Specific Manner. Biomedicines. 2020 Dec 14;8(12):608. PMID:33327466 doi:10.3390/biomedicines8120608
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