Ask about this productRelated genes to: HACE1 antibody
- Gene:
- HACE1 NIH gene
- Name:
- HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1
- Previous symbol:
- -
- Synonyms:
- KIAA1320
- Chromosome:
- 6q16.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-07
- Date modifiied:
- 2018-11-16
Related products to: HACE1 antibody
Related articles to: HACE1 antibody
- HACE1 (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1) is an antioxidant gene that plays a key role in activating antioxidant pathways to maintain cellular homeostasis. Recent studies suggest that the antioxidant gene HACE1 may be a potential therapeutic target for age-related degenerative diseases. However, its role in intervertebral disc degeneration (IDD) has not been reported in any study. To clarify the role of HACE1 in IDD, we performed in vivo and in vitro basal experiments. The MRI results indicated that the degeneration grade of intervertebral discs in old rats was significantly higher compared to that in juvenile rats. Additionally, the expression of HACE1 in the degenerated intervertebral discs of aged rats was reduced. In cellular experiments, HACE1 overexpression could restore IL-1β-induced apoptosis, mitochondrial damage and iron overload. In animal experiments, HACE1 activated antioxidant signaling pathways, attenuated oxidative stress, and increased the expression of ECM and anti-ferroptosis proteins. In summary, HACE1 alleviates the progression of IDD by inhibiting oxidative stress and ferroptosis in nucleus pulposus cells. Its protective effect may be related to the activation of the Nrf2/ARE signaling pathway. In conclusion, our results support that the antioxidant gene HACE1 could serve as a novel potential target for treating IDD. - Source: PubMed
Publication date: 2026/02/13
Xia JiyueZhang WeiJiang YouhongLi TingDong HuaizeZhu LuXia QiuqiuZhao YanYi JiangbiWeng ZijingFeng ShuaiXin Zhijun - HACE1 encodes a HECT domain and ankyrin repeat containing protein regulating several small GTPases. This protein is involved in several important functions, such as cell division, protein ubiquitination, and localization. Biallelic variants in HACE1 have been implicated in spastic paraplegia and psychomotor retardation with or without seizures (MIM: 616756). Previously, 32 patients of various ethnicities have been reported with different types of variants; loss-of-function (LoF), missense, and indels. - Source: PubMed
Publication date: 2026/02/11
Yousaf HammadAli SajidMoulvi Ahad YousufKhalid Lubaba BinteeJaved IramGhumman Rafia ZafarColson CindyIbrahim ShahnazZia SalmaKhan Muhammad MusawerBrunelle PerrineTrujillo-Quintero Juan PabloRuiz AnnaKirmani SalmanHoulden HenryToft MathiasFatima AmbrinIqbal Zafar - Pterygium syndrome is a common eye disease that often leads to vision loss and even blindness. There is increasing evidence that miRNAs play a key role in the progression of pterygium, but the function of miR-381-3p in pterygium has not been studied. Therefore, this study aimed to investigate the effect of miR-381-3p on the progression of pterygium and to elucidate its potential molecular mechanisms. Human pterygium fibroblasts (HPFs) were isolated from clinical pterygium tissues. The expression of key genes and proteins was detected via RT-qPCR and western blotting. Cell proliferation was detected by CCK-8 and scratch assay, while cell invasion was examined by Transwell assay. Protein interactions were investigated by coimmunoprecipitation. First, we found that the expression level of miR-381-3p was significantly reduced in pterygium tissues. Second, we found that the overexpression of miR-381-3p in HPFs inhibited the proliferation, migration, and invasion abilities of HPFs while inducing cell apoptosis. In addition, in pterygium tissue, the expression of MCPIP1 was downregulated, and the expression of HACE1 and TRIP12 was upregulated. Importantly, MCPIP1 interference partially attenuated the positive effects of miR-381-3p overexpression described above, and miR-381-3p could target HACE1, while HACE1 could bind to TRIP12. Mechanistic studies revealed that miR-381-3p inhibited the binding of HACE1 to TRIP12 through the inhibition of HACE1 expression, thereby inhibiting the ubiquitination and degradation of MCPIP1 and improving the progression of pterygium. Our study highlights the powerful potential of miR-381-3p in improving the progression of pterygium, laying the foundation for the development of new intervention targets for related diseases. - Source: PubMed
Publication date: 2026/01/29
Zhao YubingJi HaoHe YangZhang WeijiaXu YanzeYin YuruDu YanZhao Dandan - The CNF1 toxin from extraintestinal pathogenic (ExPEC) deamidates glutamine 61 of Rac1 small GTPase, as well as its equivalents in RhoA and Cdc42 into glutamic acid. This post-translational modification of Rho proteins abrogates the hydrolysis of GTP into GDP, thereby enhancing signal transduction. Meanwhile, the sustained GTP-loading of Rac1 Q61E sensitizes it to ubiquitin-mediated proteasomal degradation catalyzed by the HACE1 E3 ligase rate-limiting factor, leading to a cellular depletion of Rac1 over time. We report data from a quantitative genome-wide screen of siRNAs inhibiting CNF1-mediated cellular depletion of Rac1 in primary human cells. As best hits, we identified a group of three siRNAs targeting the Sec61A1 subunit of the Sec61 translocon, as well as HACE1 and the Lu/BCAM host cell receptor of CNF1. We extend these findings by identifying a group of siRNAs targeting genes involved in ER and Golgi homeostasis and trafficking. Functional studies showed that both chemical and genetic inhibition of Sec61A1 dampens GTP-loading and membrane association of Rac1 in CNF1-intoxicated cells, while the proper deamidation of RhoA provides a control of CNF1 cytosolic action. Finally, we extend these findings by showing that inhibition of -glycosylation of neo-synthesized proteins in the ER abrogates Rac1 GTP-loading in CNF1-treated cells. Collectively, these data point to a control of Rac1 signaling operated by protein biosynthesis and -glycosylation in the ER.IMPORTANCEThe remarkable evolutionary convergence of bacterial effectors from pathogens toward the host small GTPase Rac1, the master regulator of the actin cytoskeleton, confers to these microbes an enhanced capacity to invade host cells and tissues. The CNF1 toxin, a colonization factor of the gastrointestinal tract produced by pathogenic strains of has been instrumental in deciphering the regulation and function of Rac1. By performing a whole-genome screen based on CNF1 action, we establish the key requirement of Sec61 translocon-dependent protein biosynthesis and -glycosylation at the endoplasmic reticulum for proper activation of Rac1 in intoxicated cells. Our data connect the Sec61 translocon and -glycosylation of neo-synthesized proteins at the endoplasmic reticulum in the control of the activity of Rac1 and other Rho GTPases. - Source: PubMed
Publication date: 2025/10/06
Paillares EléaDeboosere NathalieDescorps-Declere StéphaneMarechal MaudGillet DanielDemangel CarolineMettouchi AmelBrodin PriscilleLemichez Emmanuel - HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1 (HACE1) is a well-known tumor suppressor and is essential for embryonic development. In recent years, researchers have increasingly discovered that HACE1 plays a vital role in the pathological process of many degenerative diseases. HACE1 is regarded as a stress-responsive gene whose expression is induced by a variety of stress stimuli. The expression of HACE1 counters cell stress damage by promoting the expression of antioxidant genes and inhibiting ROS production from Rac1-dependent NADPH oxidase. Meanwhile, HACE1 serves as a crucial E3 ubiquitin ligase that activates autophagy by ubiquitinating autophagy-related receptors to clear irreversibly oxidized biomolecules within the cell. Therefore, HACE1 is essential for cellular survival by maintaining antioxidant defense mechanisms and autophagic flux. Pharmacological and genetic modulation of HACE1 expression holds potential therapeutic value in age-related diseases such as neurodegenerative disorders, cardiovascular diseases, and cancer. - Source: PubMed
Publication date: 2025/08/29
Xia JiyueJiang YouhongXin XiangjunLi TingLiao WenboXin Zhijun