Nucleus accumbens-associated protein 1 (NAC1) (NAC1)

Nucleus accumbens-associated protein 1 (NAC1) is a BTB/POZ domain-containing transcriptional repressor that plays a pivotal role in both oncology and neuroscience [1, 3]. Originally identified in the nucleus accumbens in response to cocaine, NAC1 has since been recognized as a significant rheostat for stemness and a driver of tumor progression and chemoresistance, particularly in ovarian and breast cancers [2, 4]. It functions by modulating the expression of genes involved in the cell cycle, autophagy, and apoptosis, often through its interaction with other proteins like Cullin 3 or the pluripotency factor Oct4 [1, 4]. In cancer, high levels of NAC1 are frequently associated with poor prognosis and resistance to taxane-based therapies, making it an attractive target for therapeutic intervention [2]. While no clinical drugs currently target NAC1, experimental small molecules like NIC and natural products like Gambogic acid are being explored to disrupt its homodimerization or promote its degradation [5]. Its dual role in the central nervous system and peripheral tissues necessitates careful evaluation of potential neurological side effects during drug development [3]. Furthermore, NAC1 is involved in the maintenance of pluripotency in embryonic stem cells, suggesting that its inhibition could impact normal regenerative processes [4]. The protein's ability to form homodimers via its BTB domain is essential for its activity, providing a specific structural pocket for small-molecule targeting [1, 5].

Other names

NACC1BTBD14BBEND8Nucleus accumbens-associated 1BTB domain-containing protein 14B

Inhibition of NAC1 homodimerization or disruption of its interaction with transcriptional co-regulators and the ubiquitin-proteasome system.