HACE1

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase HACE1, HACE1, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1

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Introduction

E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases (PubMed:15254018, PubMed:21988917, PubMed:22036506, PubMed:37537642, PubMed:38332367). Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion (PubMed:21988917). Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division (PubMed:21988917). Specifically binds GTP-bound RAC1, mediating ubiquitination and subsequent degradation of active RAC1, thereby playing a role in host defense against pathogens (PubMed:22036506, PubMed:37537642, PubMed:38332367). May also act as a transcription regulator via its interaction with RARB (By similarity).

100 Clinical Results associated with HACE1

100 Translational Medicine associated with HACE1

0 Patents (Medical) associated with HACE1

120

Literatures (Medical) associated with HACE1

01 Jan 2025·Chinese Journal of Cancer Research

Improving neuroblastoma risk prediction through a polygenic risk score derived from genome-wide association study-identified loci

Article

Author: Chen, Liping ; Zhang, Xinxin ; He, Jing ; Liu, Jiabin ; Zhang, Mengzhen ; Zhang, Wenli ; Zhou, Chunlei ; Zhu, Jinhong ; Wu, Haiyan ; Chang, Jiaming

ObjectiveNeuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings. Previous genome-wide association studies (GWASs) have identified many loci associated with neuroblastoma susceptibility; however, their application in risk prediction for Chinese children has not been systematically explored. This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.MethodsWe validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children, consisting of 402 neuroblastoma patients and 473 healthy controls. Genotyping these polymorphisms was conducted via the TaqMan method. Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk. We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve (AUC) analysis. We also established a polygenic risk scoring (PRS) model for risk prediction by adopting the PLINK method.ResultsFourteen loci, including ten protective polymorphisms from CASC15, BARD1, LMO1, HSD17B12, and HACE1, and four risk variants from BARD1, RSRC1, CPZ and MMP20 were significantly associated with neuroblastoma risk. Compared with single-gene model, the 8-gene model (AUC=0.72) and 13-gene model (AUC=0.73) demonstrated superior predictive performance. Additionally, a PRS incorporating six significant loci achieved an AUC of 0.66, effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility. A higher PRS was significantly associated with advanced International Neuroblastoma Staging System (INSS) stages, suggesting its potential for clinical risk stratification.ConclusionsOur findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models, particularly the PRS, in improving risk prediction. These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.

01 Nov 2024·Neuroscience

HACE1 exerts a neuroprotective role against oxidative stress in cerebral ischemia–reperfusion injury by activating the PI3K/AKT/Nrf2 pathway

Article

Author: Liu, Xiaodan ; Jiao, Hong ; Wang, Dan ; Wang, Xiao ; Zhang, Xinyue ; Zheng, Jiaolin ; Yin, Le

HECT domain and Ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) is an E3 ubiquitin ligase involving oxidative stress, an important contributor in cerebral ischemia-reperfusion injury (CIRI). It was proposed to be associated with the PI3K/AKT pathway and Nrf2 nuclear translocation, which are important players of oxidative stress. Therefore, we supposed that HACE1 might affect CIRI by regulating the PI3K/AKT/Nrf2 pathway. Here, we used the transient middle cerebral artery occlusion-reperfusion (tMCAO/R) model to induce CIRI in rats and found lower HACE1 expression in ischemic rats compared with the control. To explore the exact role of HACE1, the lentivirus vector carrying the HACE1 sequence was administrated to rats by intracerebroventricular injection (1 × 10⁹ TU/mL, 9 μL) one week before tMCAO/R operation. HACE1 overexpression alleviated tMCAO/R-induced brain damage in rats. Further studies revealed that it reduced oxidative stress via activating the PI3K/AKT/Nrf2 pathway, thereby inhibiting neuronal apoptosis in the ischemic penumbra of rats with CIRI. Then, differentiated PC12 cells were cultured in oxygen-glucose deprivation-reoxygenation (OGD/R) conditions (OGD: 1 % O₂, 94 % N2, and 5 % CO₂; R: normal atmosphere) to simulate CIRI in vitro. Similarly, HACE1 overexpression inhibited neuronal apoptosis caused by OGD/R treatment. The PI3K inhibitor LY294002 reversed the inhibitory effects of HACE1 overexpression on oxidative stress in OGD/R-injured cells, accompanied by the inactivated AKT/Nrf2 pathway. Altogether, our results suggest that HACE1 protects against oxidative stress-induced neuronal apoptosis in CIRI by activating the PI3K/AKT/Nrf2 pathway, providing a new insight into the CIRI treatment.

01 Nov 2024·Cell Reports

ZDHHC3-mediated SCAP S-acylation promotes cholesterol biosynthesis and tumor immune escape in hepatocellular carcinoma

Article

Author: Wang, Genxin ; Wang, Fubing ; Wu, Mingzhi ; Zeng, Yiqun ; Prochownik, Edward V ; Prochownik, Edward V. ; Li, Jun ; Zhou, Xinyi ; Li, Youjun ; Zhou, Xiaojun

Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol metabolism is dysregulated is not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell cholesterol biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation by ZDHHC3 at C264 antagonizes HACE1-mediated SCAP ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates ZDHHC3 to form a positive feedback loop, which explains why negative feedback regulation of SCAP/SREBP2 signaling fails in HCC. Increased cholesterol in the tumor microenvironment (TME) restrains CD4⁺ T cell cytotoxicity. Hence, the cholesterol metabolism reprogramming and cholesterol level alternation in the TME cooperate to promote HCC development. We identified a small-molecule inhibitor of ZDHHC3 that, combined with anti-PD-1 immunotherapy, inhibited diethyl nitrosamine (DEN)/CCl₄-induced HCC growth in mice. ZDHHC3-mediated SCAP S-acylation reprograms cholesterol metabolism and promotes HCC immune escape. ZDHHC3 is thus identified as a rational chemotherapy target for HCC.

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HACE1

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