Ask about this productRelated genes to: RAC3 protein
- Gene:
- NCOA3 NIH gene
- Name:
- nuclear receptor coactivator 3
- Previous symbol:
- -
- Synonyms:
- RAC3, AIB1, ACTR, p/CIP, TRAM-1, CAGH16, TNRC16, KAT13B, bHLHe42, SRC-3, SRC3
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-17
- Date modifiied:
- 2016-10-05
- Gene:
- RAC3 NIH gene
- Name:
- Rac family small GTPase 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-11
- Date modifiied:
- 2019-04-16
Related products to: RAC3 protein
Related articles to: RAC3 protein
- Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are leading causes of cirrhosis and hepatocellular carcinoma. Defects in autophagy contribute to the development of MASLD; however, the role of Unc-51-like autophagy-activating kinase 1 (ULK1) in the pathophysiology of MASLD remains unclear. Herein, we show that ULK1, a serine/threonine kinase and core autophagy protein, is significantly repressed in human MASH livers, and that hepatocyte-specific loss of ULK1 promotes, unexpectedly, hepatic steatosis and progression to liver fibrosis, without affecting basal autophagy flux. Phospho-proteomics identified the transcriptional coactivator NCOA3 as a downstream phospho-target of ULK1. Mechanistically, ULK1 phosphorylates NCOA3 to repress its transcriptional activity and restrain the CREB/CBP-mediated de novo lipogenic program. Accordingly, a phosphorylation-deficient NCOA3 mutant drives CREB/CBP-mediated lipogenesis, whereas genetic or pharmacological NCOA3 inhibition prevents steatosis, hepatic inflammation, and profibrotic signaling. Hence, ULK1-mediated NCOA3 phosphorylation is a fundamental and druggable checkpoint against the entire MASLD spectrum. - Source: PubMed
Publication date: 2026/04/02
Koo Young DoCastillo Romilia TatianaSukumaran Nair AshaGarneau MichaelGochee ChadCampbell Zachary VVakil Tashya ShreyasHa JuaMarti AlexSoto JamieDas DebajyotiMartinez-Lopez NuriaSharma ShipraDelgado YenniferPhung CallieAshley Immy AKapelczak Edmund DJacobo RashelWeatherford Eric TDai Dao-FuBenhammou Jihane NMarshall Andrea GHinton AntentorYang LingPereira Renata OTeSlaa TaraBouhaddou MehdiSingh RajatAbel E Dale - Steroid receptor co-activators (SRCs) constitute a family of transcriptional co-regulators that comprising three structurally similar members: SRC1, SRC2 and SRC3. Although extensive research has investigated the association between SRC3 and cancer, significant knowledge gaps persist. This review summarizes current research progress, identifies existing gaps, and proposes directions for future investigations. A systematic search of the PubMed database was conducted to identify literature relevant to the this topic. The study selection process, including inclusion and exclusion criteria, is presented in the accompanying figure following PRISMA guidelines. SRC3 plays a critical role in cancer development by promoting cancer cell proliferation and growth, enhancing tumor angiogenesis, modulating immune surveillance, influencing hormone signaling, and regulating diverse cytokines, including inflammatory mediators. It has been implicated in the pathogenesis of both hormonal and non-hormonal cancers. However, a substantial gap remain in clinical trials evaluating the therapeutic potential of SRC3-targeted interventions. Although research on SRC3 in hormone-related cancers is relatively comprehensive, its role in non-hormonal cancers and its clinical translation potential remain insufficiently explored. Future research should examine how SRC3 inhibition affects immune signaling pathways, the tumor and immune microenvironments, tumor heterogeneity, and various aspects of clinical translation, including novel drug development and diagnostic model design. - Source: PubMed
Publication date: 2025/12/31
Deng XiaoliangLuo YanqunGao YingWang LiqiongWu Tao - The CREB-binding protein (CBP) and its paralogue p300 are cellular integrators of various signaling pathways involved in various physiological functions. Together with NCOA proteins, they act as coactivators of nuclear receptors. CBP/p300 and NCOA3 are overexpressed in endocrine cancers, leading to enhanced nuclear receptor activity and promoting tumor progression through activation of oncogenes and regulation of cellular functions. Thus, targeting CBP/p300-NCOA3 has great potential for the development of antitumor agents. As a tool to disrupt disease-related protein-protein interactions, we developed the NCOA3 activation domain 1 (AD1) peptide containing noncanonical α-methylated amino acids for targeting the intrinsically disordered nuclear coactivator binding domain (NCBD) in CBP/p300. We showed that this peptide variant binds with a stronger affinity to its target proteins than the wild-type peptide and inhibits CBP/p300 acetylase activity. This peptide variant also modulates interactomes and CBP/p300-mediated gene transcription and exhibits effective antiproliferative activity in cell-based assays. - Source: PubMed
Publication date: 2025/12/16
Silvestri AuroraOsz JuditJouin AlexisBauer ValentinChalhoub SandraTorbeev VladimirRochel Natacha - Breast cancer is the most common tumor in women, and approximately 70 % of cases are diagnosed to be estrogen receptor α (ERα)-positive. Estradiol (E2)-ERα signaling is undoubtedly involved in the development of breast cancer, and the upregulation of this pathway is linked to tamoxifen resistance. However, ERα regulation is complex, and the underlying mechanisms have not been comprehensively elucidated. Pin4 is a prolyl isomerase that promotes cis-trans isomerization of proline residues. Although its role remains unclear, an analysis of public databases reveals that Pin4 expression in breast cancer tissues is higher than that in normal tissues. Here, we reveal that Pin4 regulates ERα transcriptional activity and is essential for the proliferation of ERα-positive breast cancer cells. In MCF7 and T47D cells, Pin4 knockdown drastically decreased cell proliferation by inducing cell cycle arrest. In addition, the silencing of Pin4 impaired the expression of E2-induced genes, including E2F1. We also found that Pin4 interacted with ERα and affected its transcriptional activity by promoting phosphorylation at Ser167, which was involved in the recruitment of steroid receptor coactivator-3 (SRC-3) into ERα. Importantly, the silence of Pin4 gene in T47D cells attenuated the interaction between SRC-3 and ERα. Collectively, the study findings show that Pin4 is a critical factor in the development of ERα-positive breast cancers and the identification of Pin4 inhibitors could be a promising therapeutic strategy. - Source: PubMed
Publication date: 2025/08/10
Inoue Masa-KiUeda RenaNakanishi MikakoKanna MachiMatsunaga YasukaAsano TomoichiroNakatsu Yusuke - In breast cancer, adipocytes are the predominant cell type in the microenvironment, and the continuous communication between these tissues alters the adipose phenotype. However, molecular mechanisms promoting these changes are still poorly understood. Previously, we demonstrated that NCoA3 expression is increased in adipose tissue adjacent to breast cancer and that this increase is associated with an inflammatory profile. This study aimed to investigate the mechanisms underlying NCoA3 expression in adipocytes within the breast tumor microenvironment. We demonstrated that breast cancer-secreted TNF increases NCoA3 expression in adipocytes, and this upregulation is dependent on NF-κB transcriptional activity. Furthermore, the use of a TNF blocker prevented both coactivator overexpression and macrophages recruitment, mimicking the effects observed when NCoA3 expression was downregulated using a short hairpin RNA. These findings shed light on the molecular mechanisms by which breast cancer cells modulate adipocyte behavior, identifying NCoA3 as a key mediator in the tumor-adipose tissue crosstalk. Targeting this pathway through TNF inhibition offers promising therapeutic strategy to attenuate tumor-associated inflammation and potentially improve outcomes in breast cancer patients. - Source: PubMed
Publication date: 2025/05/28
Lira María CeciliaRosa Francisco DBernacchia Juliana LourdesPalma Alejandra GPaladino NataliaCostas Mónica ARubio María Fernanda