Ask about this productRelated genes to: PDCD6 antibody
- Gene:
- PDCD6 NIH gene
- Name:
- programmed cell death 6
- Previous symbol:
- -
- Synonyms:
- ALG-2, PEF1B
- Chromosome:
- 5p15.33
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-10
- Date modifiied:
- 2014-11-19
Related products to: PDCD6 antibody
Related articles to: PDCD6 antibody
- Glioblastoma is the most aggressive primary brain tumor with limited therapeutic options and poor prognosis. Understanding the genetic determinants and cellular complexity of glioblastoma is crucial for developing novel therapeutic strategies. - Source: PubMed
Publication date: 2025/10/24
Li JunXu JingDing LianshuChen Jialuo - - Source: PubMed
Publication date: 2025/08/26
Ma MingzhiLuo JuntaoLi XinDeng RuiJiang HuiHan BingsheZhang Junfang - Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a prevalent flame retardant, is associated with neurotoxicity linked to lysosomal damage. Timely repair of damaged lysosomal membranes is crucial for cell survival. This study aimed to elucidate the role of endosomal sorting complex required for transport (ESCRT)-dependent lysosomal membrane repair mechanisms in TDCPP-induced neurotoxicity, focusing on the regulatory roles of apoptosis-linked gene 2 (ALG-2) and ALG-2 interacting protein-X (ALIX) in recruiting ESCRT-III complexes. Using in vitro models of TDCPP exposure in the human neuroblastoma cell line SH-SY5Y and murine astrocyte cell line C8-D1A, we found that TDCPP exposure led to impaired lysosomal membrane repair via ESCRT-dependent mechanisms, disrupted lysosomal membrane integrity, and induced apoptosis. This impairment was characterized by: decreased expression of ALG-2, ALIX, and the ESCRT-III subunit - charged multivesicular body protein 4B (CHMP4B); reduced recruitment of CHMP4B mediated by ALG-2/ALIX; increased levels of galectin-3 and cleaved poly (ADP-ribose) polymerase (Cleaved-PARP); and an elevated apoptosis rate. Notably, ALG-2 and ALIX overexpression reinstated CHMP4B accumulation at injury sites, facilitated lysosomal recovery, and mitigated TDCPP-induced lysosomal membrane damage and apoptosis. These findings indicate that TDCPP interferes with ALG-2/ALIX-mediated ESCRT-III recruitment, leading to defective lysosomal membrane repair. Moreover, ALG-2 and ALIX overexpression attenuated TDCPP-induced lysosomal injury, enhancing cell survival. Our findings reveal a novel mechanism by which TDCPP disrupts lysosomal membrane repair through interference with ALG-2/ALIX-mediated ESCRT-III recruitment, providing the molecular mechanisms of TDCPP-induced neurotoxicity and highlighting potential therapeutic strategies for combating TDCPP toxicity. - Source: PubMed
Publication date: 2025/05/25
Li TingtingZhang YueDing XuemanLiu LiMa RunjiangQin WenqiYan ChulinWang ChunZhang JingjingKeerman MulatibiekeNiu Qiang - Lysosomes are essential membrane-bound organelles that integrate intracellular needs and external signals through multiple functions, including autophagy-mediated degradation and MTORC1 signaling. The integrity of the lysosomal membrane is therefore crucial for maintaining cellular homeostasis. Various endogenous and exogenous factors can damage lysosomes, contributing to diseases such as infections, cancer, and neurodegeneration. In response, cells mount defensive mechanisms to cope with such stress, including the formation of stress granules (SGs)-membrane-less organelles composed of RNAs and protein complexes. While SGs have emerged as key players in repairing damaged lysosomes, how lysosomal damage triggers their formation and influences cell fate remains unclear. Here we report that the calcium signal from damaged lysosomes mediates SG formation and protects cells from lysosomal damage-induced cell death. Mechanistically, calcium leakage from damaged lysosomes signals the recruitment of calcium-activating protein PDCD6IP/ALIX and its partner PDCD6/ALG2. This complex regulates protein kinase EIF2AK2/PKR and its activator PRKRA/PACT, which phosphorylates translation initiator factor EIF2S1, stalling global translation initiation. This translation arrest leads to the accumulation of inactive messenger ribonucleoprotein complexes (mRNPs), resulting in SG formation. Cells deficient in SG formation show increased cell death when exposed to lysosomal damage from disease-associated factors including SARS-CoV-2, adenovirus, malarial pigment, proteopathic MAPT/tau, or environmental hazards. Collectively, this study reveals how damaged lysosomes signal through calcium to trigger SG assembly, promoting cell survival. This establishes a novel link between membrane-bound and membrane-less organelles, with implications for diseases involving lysosome and SG dysfunction. - Source: PubMed
Publication date: 2025/02/24
Jayabalan Aravinth KumarAyeni AanuoluwakiitanJia Jingyue - - Source: PubMed
Publication date: 2025/02/11
Sun LuluWu SijinWang HuiZhang TianyuZhang MengyuBai XuepengZhang XiumeiLi BingqingZhang CaiLi YanZhou JunLi Tianliang