Ask about this productRelated genes to: KLHL9 Blocking Peptide
- Gene:
- KLHL9 NIH gene
- Name:
- kelch like family member 9
- Previous symbol:
- -
- Synonyms:
- KIAA1354, FLJ13568
- Chromosome:
- 9p21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-06-12
- Date modifiied:
- 2016-10-05
Related products to: KLHL9 Blocking Peptide
Related articles to: KLHL9 Blocking Peptide
- Distal myopathies comprise a clinically and genetically diverse group of muscle disorders characterized by initial involvement of the distal extremities. We describe siblings who developed progressive weakness in the ankle plantar flexors from adolescence to early adulthood. By their 50s, the lower legs exhibited severe fatty degeneration with pronounced involvement of the gastrocnemius and soleus. Genetic analysis identified a heterozygous p.L95F variant in KLHL9, previously associated with an early-onset autosomal dominant form of distal myopathy featuring tibialis anterior atrophy and sensory deficits. Though considering himself unaffected, the father harbored the same variant and exhibited an extremely mild phenotype. Muscle biopsy revealed chronic myopathic changes with normal expression of KLHL9. This may represent the second reported family with a KLHL9 variant, and is worth establishing KLHL9-linked distal myopathy. The combination of shared and distinct findings from the original family broadens the clinical phenotype and provides insight into the disease. - Source: PubMed
Publication date: 2025/07/26
Izumi RumikoFukasaka IsaoMatsumura TsuyoshiNakamura NaokoTakahashi ToshiakiSuzuki NaokiNishimori YukakoSugie KazumaNiihori TetsuyaAoki Masashi - Mechanistic target of rapamycin complex 1 (mTORC1) is recruited to the lysosomal membrane by the active Rag heterodimer, where mTORC1 interacts with active Rheb for its activation. It has been shown that polyubiquitination of Rheb is crucial for enhancing its interaction with mTORC1 on the lysosome. However, the specific ubiquitin ligases for Rheb, which promotes mTORC1 activation, remain elusive. We report that the CUL3-RBX1-KLHL9 E3 ubiquitin ligase complex is translocated to the lysosome and ubiquitinates Rheb in response to amino acid stimulation. KLHL9 serves as an essential adaptor for CUL3-RBX1 to target Rheb on the lysosome. Deleting either CUL3, RBX1, or KLHL9 diminishes Rheb ubiquitination and reduces amino acid-induced mTORC1 activation without impacting lysosomal mTORC1 localization or Akt activity. Thus, the CUL3-RBX1-KLHL9 complex functions as a mTORC1 activator by acting as an E3 ubiquitin ligase for Rheb and supports amino acid-induced mTORC1 activation. - Source: PubMed
Publication date: 2024/12/20
Yao YaoHong SungkiYoshida ShotaSwaroop VinamraCurtin BradyInoki Ken - () is a facultative intracellular parasitic pathogen with multiple immune escape mechanisms. Mitophagy is critical for mitochondrial quality control and function in various biological processes. We reported that infection induces mitophagy to promote its intracellular survival by decreasing mitochondrial reactive oxygen species (mtROS). Mechanically, infection leads to the rupture of host outer mitochondrial membrane (OMM) by DNM1L/DRP1 (dynamin 1-like). Furthermore, BipD, the type III secretion system (T3SS) needle tip protein of , hijacks the host KLHL9 (kelch-like 9)-KLHL13 (kelch-like 13)-CUL3 (cullin 3) E3 ubiquitin ligase complex to promote the K63-linked ubiquitination of IMMT/mitofilin (inner membrane protein, mitochondrial) at the K211 site. Then BipD-initiated mitophagy, via the conventional macroautophagy/autophagy pathway with the receptor SQSTM1 (sequestosome 1) involvement, decreases the mtROS production, which in turn facilitates the intracellular survival of . Here, our findings reveal an unexpected function of BipD and the KLHL9-KLHL13-CUL3 E3 ligase complex and suggest a novel mechanism used by bacterial pathogens that hijack host mitophagy for their survival. - Source: PubMed
Publication date: 2024/09/18
Nan DongqiMao XuhuLi Qian - Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival. - Source: PubMed
Publication date: 2024/06/04
Nan DongqiRao ChenglongTang ZhihengYang WenboWu PanChen JiangaoXia YupeiYan JingminLiu WenzhengZhang ZiyuanHu ZhiqiangChen HaiLiao YalingMao XuhuLiu XiaoyunZou QuanmingLi Qian - Interferon-γ (IFNγ) is a critical mediator of cell-intrinsic immunity to intracellular pathogens. Understanding the complex cellular mechanisms supporting robust interferon-γ-induced host defenses could aid in developing new therapeutics to treat infections. Here, we examined the impact of autophagy genes in the interferon-γ-induced host response. We demonstrate that genes within the autophagy pathway including , , and , as well as ubiquitin ligase complex genes and are required for IFNγ-induced inhibition of murine norovirus (norovirus hereinafter) replication in mouse cells. and were also required for IFNγ-mediated restriction of parasite growth within the parasitophorous vacuole in human cells. Furthermore, we found that perturbation of UFMylation pathway components led to more robust IFNγ-induced inhibition of norovirus via regulation of endoplasmic reticulum (ER) stress. Enhancing or inhibiting these dynamic cellular components could serve as a strategy to control intracellular pathogens and maintain an effective immune response. - Source: PubMed
Publication date: 2023/10/31
McAllaster Michael RBhushan JayaBalce Dale ROrvedahl AnthonyPark ArnoldHwang SeungminSullender Meagan ESibley L DavidVirgin Herbert W