Ask about this productRelated genes to: KIAA0226 antibody
- Gene:
- RUBCN NIH gene
- Name:
- rubicon autophagy regulator
- Previous symbol:
- KIAA0226
- Synonyms:
- rubicon, rundataxin
- Chromosome:
- 3q29
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-21
- Date modifiied:
- 2019-04-23
- Gene:
- RUBCNL NIH gene
- Name:
- rubicon like autophagy enhancer
- Previous symbol:
- C13orf18, KIAA0226L
- Synonyms:
- FLJ21562, PACER
- Chromosome:
- 13q14.13
- Locus Type:
- gene with protein product
- Date approved:
- 2003-02-20
- Date modifiied:
- 2018-12-21
Related products to: KIAA0226 antibody
Related articles to: KIAA0226 antibody
- Nearly fifty million older people suffer from neurodegenerative diseases, including Alzheimer (AD) and Parkinson (PD) disease, a global burden expected to triple by 2050. Such an imminent "neurological pandemic" urges the identification of environmental risk factors that are hopefully avoided to fight the disease. In 2022, strong evidence in mouse models incriminated defective lysosomal acidification and impairment of the autophagy pathway as modifiable risk factors for dementia. To date, the most prescribed lysosomotropic drugs are proton pump inhibitors (PPIs), chloroquine (CQ), and the related hydroxychloroquine (HCQ), which belong to the group of disease-modifying antirheumatic drugs (DMARDs). This commentary aims to open the discussion on the possible mechanisms connecting the long-term prescribing of these drugs to the elderly and the incidence of neurodegenerative diseases.: AD: Alzheimer disease; APP-βCTF: amyloid beta precursor protein-C-terminal fragment; BACE1: beta-secretase 1; BBB: brain blood barrier; CHX: Ca/H exchanger; CMI: cognitive mild impairment; CQ: chloroquine; DMARD: disease-modifying antirheumatic drugs; GBA1: glucosylceramidase beta 1; HCQ: hydroxychloroquine; HPLC: high-performance liquid chromatography; LAMP: lysosomal associated membrane protein; MAPK/JNK: mitogen-activated protein kinase; MAPT: microtubule associated protein tau; MCOLN1/TRPML1: mucolipin TRP cation channel 1; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NRBF2: nuclear receptor binding factor 2; PANTHOS: poisonous flower; PD: Parkinson disease; PIK3C3: phosphatIdylinositol 3-kinase catalytic subunit type 3; PPI: proton pump inhibitor; PSEN1: presenilin 1, RUBCN: rubicon autophagy regulator; RUBCNL: rubicon like autophagy enhancer; SQSTM1: sequestosome 1; TMEM175: transmembrane protein 175; TPCN2: two pore segment channel 2; VATPase: vacuolar-type H-translocating ATPase; VPS13C: vacuolar protein sorting ortholog 13 homolog C; VPS35: VPS35 retromer complex component; WDFY3: WD repeat and FYVE domain containing 3; ZFYVE1: zinc finger FYVE-type containing 1. - Source: PubMed
Publication date: 2023/07/23
Giuliano SandyMontemagno ChristopherDomdom Marie-AngelaTeisseire ManonBrest PatrickKlionsky Daniel JHofman PaulPagès GillesMograbi Baharia - Post-translational modifications, such as phosphorylation, ubiquitination and acetylation, play crucial roles in the regulation of autophagy. Acetylation has emerged as an important regulatory mechanism for autophagy. Acetylation regulates autophagy initiation and autophagosome formation by targeting core components of the ULK1 complex, the BECN1-PIK3C3 complex, and the LC3 lipidation system. Recent studies have shown that acetylation occurs on the key proteins participating in autophagic cargo assembly and autophagosome-lysosome fusion, such as SQSTM1/p62 and STX17. In addition, acetylation controls autophagy at the transcriptional level by targeting histones and the transcription factor TFEB. Here, we review the current knowledge on acetylation of autophagy proteins and their regulations and functions in the autophagy pathway with focus on recent findings. ACAT1: acetyl-CoA acetyltransferase 1; ACSS2: acyl-CoA synthetase short chain family member 2; AMPK: AMP-activated protein kinase; ATG: autophagy-related; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCAR2/DBC1: cell cycle and apoptosis regulator 2; BECN1: beclin 1; CMA: chaperone-mediated autophagy; CREBBP/CBP: CREB binding protein; EP300/p300: E1A binding protein p300; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3: glycogen synthase kinase 3; HDAC6: histone deacetylase 6; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; KAT2A/GCN5: lysine acetyltransferase 2A; KAT2B/PCAF: lysine acetyltransferase 2B; KAT5/TIP60: lysine acetyltransferase 5; KAT8/MOF: lysine acetyltransferase 8; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; PD: Parkinson disease; PE: phosphatidylethanolamine; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PKM2: pyruvate kinase M1/2; PtdIns3P: phosphatidylinositol-3-phosphate; PTM: post-translational modification; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RUBCN/Rubicon: rubicon autophagy regulator; RUBCNL/Pacer: rubicon like autophagy enhancer; SIRT1: sirtuin 1; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylamide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TFEB: transcription factor EB; TP53/p53: tumor protein p53; TP53INP2/DOR: tumor protein p53 inducible nuclear protein 2; UBA: ubiquitin-associated; ULK1: unc-51 like autophagy activating kinase 1; VAMP8: vesicle associated membrane protein 8; WIPI2: WD repeat domain, phosphoinositide interacting 2. - Source: PubMed
Publication date: 2022/04/18
Xu YinfengWan Wei - Recently, we identified a vertebrate-specific macroautophagy/autophagy regulator, RUBCNL/Pacer, which promotes autolysosome formation by engaging the class III phosphatidylinositol 3-kinase (PtdIns3K) and HOPS complexes. Hepatocyte-specific rubcnl knockout in mice results in impaired autophagy flux, glycogen and lipid accumulation, and liver fibrosis. We further showed that under nutrient-rich conditions RUBCNL is inactivated by MTORC1-mediated phosphorylation. When nutrients are insufficient, RUBCNL is dephosphorylated, which facilitates its acetylation by the activated GSK3-KAT5/TIP60 pathway. RUBCNL acetylation significantly enhances HOPS complex recruitment, which eventually results in more efficient autophagosome maturation and lipid metabolism both in vitro and in vivo. Therefore, our work not only demonstrates that RUBCNL is essential for hepatic autophagy and liver homeostasis, but also reveals a signal integration mechanism involved in late stages of autophagy and lipid metabolism. Interestingly, these in vitro and in vivo functional data on RUBCNL are partially the opposite of the results from RUBCN/Rubicon studies that were either obtained by us or others. This implies a dual molecular switch model that is controlled by RUBCNL and RUBCN in modulation of autophagosome maturation and lipid metabolism. - Source: PubMed
Publication date: 2019/03/27
Cheng XiaweiSun Qiming - Class III PI3-kinase (PI3KC3) is essential for autophagy initiation, but whether PI3KC3 participates in other steps of autophagy remains unknown. The HOPS complex mediates the fusion of intracellular vesicles to lysosome, but how HOPS specifically tethers autophagosome to lysosome remains elusive. Here, we report Pacer (protein associated with UVRAG as autophagy enhancer) as a regulator of autophagy. Pacer localizes to autophagic structures and positively regulates autophagosome maturation. Mechanistically, Pacer antagonizes Rubicon to stimulate Vps34 kinase activity. Next, Pacer recruits PI3KC3 and HOPS complexes to the autophagosome for their site-specific activation by anchoring to the autophagosomal SNARE Stx17. Furthermore, Pacer is crucial for the degradation of hepatic lipid droplets, the suppression of Salmonella infection, and the clearance of protein aggregates. These results not only identify Pacer as a crucial multifunctional enhancer in autophagy but also uncover both the involvement of PI3KC3 and the mediators of HOPS's specific tethering activity in autophagosome maturation. - Source: PubMed
Cheng XiaweiMa XiulingDing XianmingLi LinJiang XiaoShen ZhirongChen SheLiu WeiGong WeihuaSun Qiming