Ask about this productRelated genes to: RB1CC1 Blocking Peptide
- Gene:
- RB1CC1 NIH gene
- Name:
- RB1 inducible coiled-coil 1
- Previous symbol:
- -
- Synonyms:
- KIAA0203, Cc1, DRAGOU14, FIP200, ATG17, PPP1R131
- Chromosome:
- 8q11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-01
- Date modifiied:
- 2016-11-01
Related products to: RB1CC1 Blocking Peptide
Related articles to: RB1CC1 Blocking Peptide
- Parkinson disease (PD), the second most common neurodegenerative disorder, is pathologically linked to dysregulated autophagy, a conserved lysosomal degradation pathway. Current conventional PD therapies are often limited by significant side effects, underscoring the demand for alternative treatment strategies. Drug repurposing of FDA-approved compounds represents a promising approach to address this unmet clinical need. Here, by integrating clinical data analysis, we identified an association between autophagy impairment and specific PD patient subtypes, suggesting that ULK1-dependent autophagy activation may offer therapeutic benefit. Through systematic screening for autophagy induction and neuroprotective activity, we identified econazole, a known imidazole antifungal, as a promising candidate. Econazole exhibited robust therapeutic effects across multiple PD models, including MPTP-induced zebrafish and mouse models, as well as SNCA mutant mouse models. Notably, its efficacy was dependent on functional autophagy, as autophagy inhibition abrogated its beneficial effects. Mechanistically, econazole activated ULK1, enhanced autolysosome formation, and promoted clearance of SNCA aggregates. Mouse brain microarray analysis indicated that econazole-activated ULK1 suppresses MAP3K12/DLK-MAPK8/JNK-MAPK9/JNK2-mediated neuronal apoptosis. Further phosphoproteomic profiling uncovered a novel ULK1-HSPA8/Hsc70 interaction that promotes LAMP1 and LAMP2 activation and enhances lysosomal function. This ULK1-HSPA8 complex additionally activated the BECN1 (beclin 1) complex to facilitate autophagosome formation. Together, our findings highlight a clinical data-guided drug repurposing approach that identifies econazole as a potent autophagy activator with therapeutic efficacy in ULK1-linked PD models, opening new avenues for PD treatment.: 3-MA: 3-methyladenine; ACTB: actin beta; ATG: autophagy related; AUC: area under the curve; BafA1: bafilomycin A1; BECN1: beclin 1; CMA: chaperone-mediated autophagy; DA: dopamine; DOPAC: 3,4-dihydroxyphenylacetic acid; Econ: econazole; GFP: green fluorescent protein; HEK-293T: human embryonic kidney 293T; HSPA8: heat shock protein 8 family A (Hsp70) member 8; HVA: homovanillic acid; JUN: Jun proto-oncogene, AP-1 transcription factor subunit; KSEA: kinase-substrate enrichment analysis; LAMP: lysosome associated membrane protein; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP2K: mitogen-activated protein kinase kinase; MAP3K12: mitogen-activated protein kinase kinase kinase 12; MAPK: mitogen-activated protein kinase; MPP+: 1-methyl-4-phenylpyridinium; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD: Parkinson disease; RB1CC1: RB1 inducible coiled-coil 1; RFP: red fluorescent protein; RMSD: root mean square deviation; SEM: standard error of the mean; SNCA: synuclein alpha; SQSTM1: sequestosome 1; SYP: synaptophysin; TFEB: transcription factor EB; TH: tyrosine hydroxylase; ULK1: unc-51 like autophagy activating kinase 1; WT: wild-type. - Source: PubMed
Publication date: 2026/05/17
Zhang JinJin WenkeFu YuqiZhen YongqiChen YanmeiLiu WeiHuang WeiWang ZhiwenZhu Hong-PingYang Qian-QianZhan GuZhao QianPeng ChengZhang LanHan BoLiu Bo - ATG16L1 (autophagy related 16 like 1) is a core macroautophagy/autophagy protein essential for autophagosome formation. It also functions in non-canonical autophagy pathways such as LC3-associated phagocytosis (LAP) and in other processes including immunity, inflammation, and membrane trafficking. This review synthesizes recent advances and proposes that ATG16L1 functions as a central molecular integrator governed by a multi-layered regulatory code. This framework includes genetic polymorphisms, transcriptional control, and diverse post-transcriptional and post-translational mechanisms. We detail how these regulatory layers collectively fine-tune ATG16L1 function in response to cellular stress. Dysregulation of this network contributes broadly to human diseases including inflammatory bowel disease, cancer, and neurodegenerative disorders. Notably, the functional impact of specific regulatory events is highly context dependent, a principle exemplified by the Crohn disease-associated T300A polymorphism. Deciphering this regulatory landscape and its crosstalk with both autophagy-dependent and autophagy-independent functions positions ATG16L1 as a pivotal node in cellular homeostasis and as an emerging therapeutic target. ATG: autophagy related; CASM: conjugation of Atg8-family proteins to single membranes; CCD: coiled-coil domain; CEBPA/CEBPα: CCAAT enhancer binding protein alpha; CHUK/IKKA: component of inhibitor of nuclear factor kappa B kinase complex; circRNA: circular RNA; CPT1A: carnitine palmitoyltransferase 1A; CREB: cAMP responsive element binding protein; CSNK2: casein kinase 2; FTO: FTO alpha-ketoglutarate dependent dioxygenase; GJA8/connexin 50: gap junction protein alpha 8; H/R: hypoxia-reoxygenation; HDAC: histone deacetylase; KAT2B/PCAF: lysine acetyltransferase 2B; KDM1A: lysine demethylase 1A; LAP: LC3-associated phagocytosis; lncRNA: long non-coding RNA; LRRK2: leucine rich repeat kinase 2; mA: N6-methyladenosine; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; miRNA/MIR: microRNA; Mtb: ; ncRNA: non-coding RNA; PE: phosphatidylethanolamine; PI3K: phosphoinositide 3-kinase; PRKA/PKA: protein kinase cAMP-activated; PPP1: protein phosphatase 1; RAB33B: RAB33B, member RAS oncogene family; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SETD7: SET domain containing 7, histone lysine methyltransferase; SQSTM1/p62: sequestosome 1; TNF/TNF-α: tumor necrosis factor; ULK: unc-51 like autophagy activating kinase; V-ATPase: vacuolar-type H-translocating ATPase; VDR: vitamin D receptor; WIPI2B: WD repeat domain, phosphoinositide interacting 2B; YTHDF2: YTH N6-methyladenosine RNA binding protein F2; ZDHHC7: zDHHC palmitoyltransferase 7. - Source: PubMed
Publication date: 2026/05/14
Wei FujingLiu ZhenzhenYu XiaoyingSun YinqiZhao YuanyuanWang YuFeng ZilingZhao XiaozhuKe XiaoxueYang AiminCui Hongjuan - Di(2-ethylhexyl) phthalate (DEHP) is a widely used industrial plasticizer, raising global concerns due to its potential endocrine-disrupting effects and environmental persistence. Human exposure to DEHP primarily occurs through the ingestion of contaminated food and water, inhalation of airborne particles, and dermal contact with products containing DEHP. Understanding the toxicological mechanisms of DEHP is essential for evaluating its health risks and developing effective strategies to mitigate its adverse effects. In this study, we conducted long-term exposure experiments to DEHP using both an animal model and in vitro system to investigate the complex interplay among DNA methylation, hyperactivation of macroautophagy/autophagy, mitochondrial dysfunction, and lipid accumulation induced by DEHP. The results revealed that DEHP exposure induced the degradation of DNMT1 (DNA methyltransferase 1) by enhancing its interaction with the autophagy-related protein SQSTM1 (sequestosome 1). DNMT1 degradation resulted in decreased methylation of the promoter regions of genes associated with autophagosome formation, subsequently increasing their expression. The resulting demethylation excessively activated autophagy, contributing to mitochondrial dysfunction and lipid accumulation in the liver. This study uncovered a previously unrecognized interplay among hyperactivation of autophagy, mitochondrial dysfunction, and lipid accumulation in the context of DEHP exposure. These findings enhanced our understanding of DEHP's toxicity and underscored concerns about the long-term health effects of environmental pollutants, particularly regarding metabolic diseases. ATG5:autophagy related 5; ATG16L1: autophagy related 16 like 1; BECN1:beclin 1; COX4/COXIV: cytochrome c oxidase subunit 4; BS-seq:bisulfite sequencing; DCFH-DA: 2',7'-dichlorodihydrofluoresceindiacetate; DEHP: di(2-ethylhexyl) phthalate; DNMT1: DNAmethyltransferase 1; DNMT3A: DNA methyltransferase 3A; FABP4: fattyacid binding protein 4; FASN: fatty acid synthase; LPL: lipoproteinlipase; MAP1LC3/LC3: microtubule associated protein1 light chain 3; NAFLD: nonalcoholic fatty liver disease; NR1H3:nuclear receptor subfamily 1 group H member 3; PPARG: peroxisomeproliferator activated receptor gamma; RB1CC1: RB1 induciblecoiled-coil 1; SQSTM1: sequestosome 1; SREBF2: sterol regulatoryelement binding transcription factor 2; VDAC1: voltage dependentanion channel 1. - Source: PubMed
Publication date: 2026/05/06
Yu Si-YuLiu QiaoGu Yao-HuaHan Wen-ZhuoHan Ao-JingXiong JunLi Tian-ZhouHu Qiu-ShuangGang Fang-YingZhao Chen-QianFeng TianTian JianboMiao XiaopingYu Xue-JieXie Neng-BinYuan Bi-Feng - Natural products are biologically active compounds used for therapeutic interventions for various diseases, particularly infections. Autophagy is an intracellular catabolic pathway involving lysosomal degradation and is closely associated with immunological pathways, effectively combating bacterial, viral, fungal, and parasitic infections. Accumulating evidence suggests that autophagy activation or inhibition by natural products promotes antimicrobial responses against various pathogens. Numerous natural products can modulate autophagy through diverse signaling pathways, suggesting their potential as a host-directed therapeutic strategy that may complement conventional drug regimens or help mitigate drug resistance in various infectious diseases. However, it remains largely unclear whether these effects are mediated by direct modulation of autophagy or indirectly through associated mechanisms, including enhanced immune defense, attenuation of pathological inflammation, or crosstalk with other organelle functions. Additionally, multiple pathogens can evade host responses; thus, autophagy activation may inadvertently create favorable conditions for certain pathogens. This review discusses the current knowledge of natural products in terms of their antimicrobial actions through autophagy regulation, particularly the roles of distinct natural product classes, such as polyphenols, alkaloids, terpenoids, quinones, peptides, and macrolides in modulating autophagy for potentially contributing to control various infectious diseases. Exploring the intricate molecular interplay between natural products and autophagy in limiting infections may provide valuable insights that could inform the development of innovative host-directed antimicrobial treatments based on autophagy regulation. 3-MA: 3-methyladenine; AM: alveolar macrophages; AMP: antimicrobial peptides; AMPK: 5' adenosine monophosphate-activated protein kinase; ARDS: acute respiratory distress syndrome; ART: artemisinin; ASFV: African swine fever virus; ATG: autophagy related; AZM: azithromycin; BafA1: bafilomycin A; BECN1: beclin 1; BMDM: bone marrow-derived macrophage; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2; CBD: cannabidiol; CF: cystic fibrosis; CGA: chlorogenic acid; CGAS: cyclic GMP-AMP synthase; CHUK/IKKα: component of inhibitor of nuclear factor kappa B kinase complex; CLP: cecal ligation and puncture; CLR: clarithromycin; CMA: chaperone-mediated autophagy; CoV: coronavirus; DHT: dihydrotanshinone I; EGCG: epigallocatechin-3-gallate; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK2: eukaryotic translation initiation factor 2 alpha kinase 2; ESKAPE: , and spp.; ESRRA: estrogen related receptor alpha; FOXO1: forkhead box O1; FUNDC1: FUN14 domain containing 1; HBV: hepatitis B virus; HCV: hepatitis C virus; HDT: host-directed therapy; HIV: human immunodeficiency virus; HMGB1: high mobility group box 1; HSV: herpes simplex virus; IAV: influenza A virus; ICT: isocryptotanshinone; IFN: interferon; IKBKB/IKKβ: inhibitor of nuclear factor kappa B kinase subunit beta; IL: interleukin; INH: isoniazid; IRF3: IFN regulatory factor 3; KEAP1: kelch like ECH associated protein 1; LAMP: lysosomal associated membrane protein; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MDM: monocyte-derived macrophage; MDR: multidrug-resistant; MON: monotropein; Mtb: ; MTOR: mechanistic target of rapamycin kinase; mtROS: mitochondrial ROS; NET: neutrophil extracellular trap; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NFKB/NF-κB: nuclear factor kappa B; NLRP3: NLR family pyrin domain containing 3; NLRX1: NLR family member X1; NOTCH1: notch receptor 1; NTM: nontuberculous mycobacteria; OMS: ohmyungsamycin; PAK1: p21 (RAC1) activated kinase 1; PINK1: PTEN induced kinase 1; PKM/PKM2: pyruvate kinase M1/2; PLD: phospholipase D; PM: peritoneal macrophage; PPM1A: protein phosphatase, Mg2+/Mn2+ dependent 1A; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PTEN: phosphatase and tensin homolog; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RELA/p65: RELA proto-oncogene, NF-kB subunit; RIF: rifampicin; ROS: reactive oxygen species; RSV: resveratrol; RUBCN/rubicon: rubicon autophagy regulator; SAR: selective autophagy receptor; SIRT: sirtuin; STING1: stimulator of interferon response cGAMP interactor 1; STX17: syntaxin 17; Tat: trans-activator of transcription; TB: tuberculosis; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TLR: toll like receptor; TNA: tanshinone IIA; TNF: tumor necrosis factor; UA: ursolic acid; ULK1/Atg1: unc-51 like autophagy activating kinase 1; UPR: unfolded protein response; UVRAG: UV radiation resistance associated; VAMP8: vesicle associated membrane protein 8; VDR: vitamin D receptor; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1; ZIKV: Zika virus. - Source: PubMed
Publication date: 2026/04/28
Paik SeungwhaUm SoohyunKim In SooPark Eun-JinKim Kyung TaeBasu JoyotiOh Dong-ChanJo Eun-Kyeong - Macroautophagy/autophagy is a critical cellular process that maintains the cellular homeostasis by degrading and recycling cytotoxic material. Despite its importance, the intricate mechanisms governing this process remain partially elusive. Here, we designed and performed a genome-wide loss-of-function screen on a mouse haploid ESC mutant library and identified the actin-binding protein CORO1C (coronin 1C) as a previously unrecognized regulator of mammalian autophagy. Interactions between CORO1C and the ACTR2/ARP2 (actin related protein 2)-ACTR3/ARP3 complex are essential for branched actin network assembly, SQSTM1/p62 body formation, and maintaining autophagosome structural integrity. Unlike CORO1A and CORO1B, CORO1C possesses a unique second actin-binding site involved in regulating the branched actin network and autophagic process. Notably, newborn mice died earlier in starvation than wild-type littermates and multiple tissues showed autophagy-deficient phenotypes. Moreover, the adult -deficient mice exhibit severe spatial learning memory impairment. Collectively, our research uncovered the surprising role of CORO1C in promoting the formation of branched actin network and its central role in the assembly of structures vital to autophagy.: ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ARPC2: actin related protein 2/3 complex, subunit 2; ATG: autophagy related; ATG5: autophagy related 5; BafA1: bafilomycin A; CQ: chloroquine; FACS: fluorescence-activated cell sorting; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; haESC: haploid embryonic stem cell; HML: haploid-mutant library; IF: immunofluorescence; KO: knockout; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3B; RB1CC1/FIP200: RB1-inducible coiled-coil 1; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TEM: transmission electron microscopy; WB: western blotting; WT: wild type. - Source: PubMed
Publication date: 2026/04/20
Zhang GuozhongYu NingqingSun YiLi XiaowenSun LihongLiu GuangHuang Yue