Ask about this productRelated genes to: HAX1 Blocking Peptide
- Gene:
- HAX1 NIH gene
- Name:
- HCLS1 associated protein X-1
- Previous symbol:
- -
- Synonyms:
- HS1BP1, HCLSBP1
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-05-19
- Date modifiied:
- 2019-04-23
Related products to: HAX1 Blocking Peptide
Related articles to: HAX1 Blocking Peptide
- HS-1-associated protein X-1 (HAX-1) is a ubiquitously expressed, multifunctional protein that regulates Ca homeostasis and cell survival in cardiac muscle. In addition to its well-established anti-apoptotic function, HAX-1 has recently been implicated in autophagy regulation. In the present study, we explored the molecular mechanisms underlying HAX-1-mediated autophagy modulation in cellular models, including cardiac-derived H9c2 myotubes. HAX-1 overexpression enhanced autophagic activity, as evidenced by decreased sequestosome-1 (p62), increased microtubule-associated protein light chain 3-II (LC3-II), enhanced LC3 puncta formation, and elevated autophagic flux. Conversely, HAX-1 knockdown attenuated autophagic activity. Mechanistically, co-immunoprecipitation assays showed that HAX-1 associates with both p62 and LC3. Bioinformatic analysis of the HAX-1 protein sequence identified two conserved LC3-interacting region (LIR) motifs within its N-terminal domain. Deletion of this LIR-containing region (HAX-1ΔLIR) reduced LC3 association, decreased autophagic activity, and impaired autophagy-dependent clearance of HAX-1 itself following autophagy induction, suggesting the importance of these motifs. At a cardiac-relevant level, HAX-1 promoted a chloroquine-sensitive reduction in protein levels of its known binding partner, phospholamban (PLN), a key regulator of sarcoplasmic reticulum (SR) Ca cycling. These findings indicate a previously unrecognized LC3/LIR-dependent mechanism underlying HAX-1-mediated autophagy modulation and suggest a potential role for HAX-1 in SR protein proteostasis. - Source: PubMed
Publication date: 2026/08/14
Vafiadaki ElizabethPapadopoulos PanagiotisEliopoulos Aristides GSanoudou Despina - Hepatocellular carcinoma (HCC) remains a malignancy with poor prognosis and limited therapeutic targets. Emerging evidence suggests a critical role for iron metabolism and ferroptosis in tumor progression. However, the involvement of hematopoietic lineage cell-specific protein 1 (HAX1) in HCC, particularly its regulatory role in ferroptosis, remains largely unknown. Here, we report that HAX1 is significantly upregulated in HCC tissues and correlates with advanced pathological stages and poor patient survival, suggesting its potential as an oncogene. Functionally, HAX1 overexpression promotes the proliferation and migration of HCC cells, while its knockdown inhibits these malignant phenotypes. Mechanistically, we demonstrate that HAX1 acts as a negative regulator of ferroptosis. Silencing HAX1 sensitizes HCC cells to the ferroptosis inducer IKE, leading to abnormal accumulation of intracellular ferrous iron (Fe) and increased lipid reactive oxygen species (ROS). Conversely, HAX1 overexpression suppresses iron overload and lipid peroxidation. Furthermore, we reveal that HAX1 maintains redox homeostasis by regulating the GSH/GPX4 antioxidant pathway. Knockdown of HAX1 depletes reduced glutathione (GSH), reduces glutathione peroxidase activity, and downregulates key ferroptosis defense proteins, including GPX4, FSP1, and SLC7A11. Our findings identify HAX1 as a critical promoter of HCC progression that functions by inhibiting ferroptosis through the modulation of iron homeostasis and the GSH/GPX4 pathway. Targeting the HAX1-mediated anti-ferroptotic mechanism may represent a promising therapeutic strategy for HCC treatment. - Source: PubMed
Publication date: 2026/07/01
Guo YueyueZhou YutingWu JingZhou JizheZhu MiaomiaoXie DelongYi SanguiLiu Zongling - The anti-apoptotic genes DAD-1 and HAX-1 and the pro-apoptotic GZMB gene have a significant role in the regulation of apoptosis in heart tissue. However, investigation into these genes and their proteins in the pathogenesis of cardiovascular diseases remains limited. The aim was to characterize the association between the presence and distribution of pro-apoptotic and anti-apoptotic genes and their proteins in the right atrial appendage affected by coronary heart disease (CHD) and aortic valve stenosis (AoS) and to compare the findings with those of the control group. Tissue was obtained from the right atrial appendage of 15 patients with CHD and AoS during elective open-heart surgeries. Control samples were collected from 5 pediatric individuals from archival material held in the historical anatomy collection. Tissue samples were stained with H&E for routine examination. The HAX-1 and GZMB proteins were detected by immunohistochemistry, while CISH was used to identify HAX-1, GZMB, and DAD-1 genes. The results were evaluated semi-quantitatively and analyzed using the Mann-Whitney U test and Spearman's correlation coefficient. The patients exhibited a moderate number of cardiomyocytes positive for HAX-1 and GZMB proteins, while controls displayed numerous to abundant positive cells. The DAD-1 gene was equally expressed in controls and patients, while HAX-1 and GZMB-positive cells were predominant in the control tissue. A statistically significant difference in positive HAX-1 gene cardiomyocytes was observed between the patients and controls only. A positive correlation was detected between the expression of the HAX-1 gene and the corresponding HAX-1 protein. The decreased expression of the HAX-1 gene and a tendency toward reduced GZMB gene expression in patient tissue may reflect, at least in part, an apparent balance in apoptosis-related expression patterns associated with GZMB and HAX-1 in cases of CHD and AoS, with potential contributions from age- and disease-related differences. The use of both CISH and IHC analyses provided complementary assessment of the observed findings. Additionally, no differences were found in DAD-1 gene expression between control and CHD/AoS-affected cardiomyocytes, which may reflect a less prominent or variable role of this gene in the studied conditions. - Source: PubMed
Publication date: 2026/06/13
Zaharovs VitalijsPilmane Mara - The multicellular metazoan lineage acquired a novel chaperone in the mitochondrial intermembrane space, the AAA+ disaggregase and refoldase CLPB. Although it is not known how they function together, CLPB and the intrinsically disordered IMS protein HAX1 interact and share disease and cellular phenotypes; loss of function in either gene causes severe congenital neutropenia as well as neuropathology and causes many proteins in the IMS and its bounding membranes to become insoluble. Through biochemical reconstitution, we here find that HAX1 is a direct stimulatory cofactor of CLPB. HAX1 promotes oligomerization of CLPB into an active disaggregase and stimulates the ATPase and refoldase activities of the oligomeric complex. A short peptide within HAX1 is necessary for direct interaction with the ankyrin domain of CLPB, but stimulation of CLPB activity requires additional elements of HAX1. Characterization of CLPB and CLPB-HAX1 oligomers indicates that HAX1 shifts the predominant oligomeric state of CLPB from a dodecamer to an apparent hexamer elaborated with HAX1, suggesting that this smaller oligomer is important during the cycle of CLPB function with clients. - Source: PubMed
Publication date: 2026/08/09
Fahie Monifa A VHoffman Julia GKay Mimi SKardon Julia R - Severe congenital neutropenia (SCN) is a rare hematological disorder characterized by a marked reduction in circulating neutrophils and recurrent infections. This study aimed to evaluate bone metabolism in patients with SCN via biochemical and bone mineral density (BMD) measurements. This study included 76 patients who were diagnosed with SCN at six tertiary immunology centers. Demographic, clinical, laboratory, and BMD findings were retrospectively analyzed and measured via dual-energy X-ray absorptiometry (DXA). The study included 76 patients, 39 (51.3%) females and 37 (48.7%) males. The mean age was 206.9 ± 105.1 months, with a median age at diagnosis of 18.5 months (range: 1-264) and a follow-up period of 120 months (range: 2-324). Parental consanguinity was present in 57 patients (75%). Among patients evaluated by DXA, 30 (39.5%) had low BMD, with a mean BMD score of 0.63 ± 0.20 and a Z-score of -2.88 ± 0.90. Osteoporosis was detected in 11 adult patients (29.7%). The most common genetic mutations were HAX1 in 46 patients (60.5%) and ELANE in 15 patients (19.7%). No significant difference in BMD was observed between patients with HAX1 and ELANE mutations (p = 0.60). Granulocyte colony-stimulating factor (G-CSF) was administered to 73 patients. The median G-CSF dose was 5 (2-12) µg/kg/day in the normal BMD group and 5 (2-10) µg/kg/day in the low BMD group. No significant relationship was found between the duration or dose of G-CSF and BMD (p = 0.76, p = 0.38). Additionally, 13 patients received vitamin D, four received calcium, and one was treated with calcitonin and alendronate. Our findings indicate that patients with SCN have a high prevalence of bone mineral loss. The underlying pathophysiology and potential effects of recombinant G-CSF treatment on increased bone mineral loss remain controversial and warrant further investigation. - Source: PubMed
Publication date: 2026/05/24
Karali YasinAyvaz Deniz CagdasKarapinar Deniz YilmazMetin AyseAydiner Elif KarakocKose HulyaCaka CananKaradas NihalDemir Kezban IpekOzen Ahmet OguzhanYuksek MutluOngen Yasemin DenkboyKilic Sara Sebnem