Ask about this productRelated genes to: Atg12 Blocking Peptide
- Gene:
- ATG12 NIH gene
- Name:
- autophagy related 12
- Previous symbol:
- APG12L
- Synonyms:
- APG12
- Chromosome:
- 5q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-01
- Date modifiied:
- 2016-10-05
Related products to: Atg12 Blocking Peptide
Related articles to: Atg12 Blocking Peptide
- The macroautophagy/autophagy machinery has two ubiquitin-like (UBL) conjugation systems. The Atg8/MAP1LC3/GABARAP (yeast/human) and Atg12/ATG12 proteins are UBL substrates for Atg7/ATG7, a non-canonical E1 enzyme, that thioesterifies its substrates; however, autophagy requires a much greater amount of conjugated Atg8 (Atg8-PE) than Atg12 (Atg12-Atg5). Exactly how Atg7/ATG7 distinguishes between its two substrates to facilitate this differential biogenesis remains elusive. Here, analyses of recombinant complexes of yeast proteins reveal that the N termini of Atg8 and Atg12 are structural determinants for conjugation to Atg7, but play no role in conjugation to Atg3 or Atg10, non-canonical E2 enzymes. The disordered N terminus of Atg12 is a protector of the Atg12 C terminus and a negative regulator of Atg7-Atg12 conjugation and autophagy, whereas the N-terminal helical domain in Atg8 promotes autophagy and has a high avidity to Atg7. We show that balanced autophagy requires different specific N termini attached to the UBL domains, which are structural determinants for selective transfer to the native E2s. These findings deepen our understanding of the two autophagy UBL conjugation systems that is far from complete. - Source: PubMed
Publication date: 2026/05/15
Popelka HanaKlionsky Daniel J - Accurate identification of which patients with early (T1) colon cancer (CC) have lymph node metastases (LNM) is a major challenge. Current strategies have limited accuracy, resulting in overtreatment of > 80% of patients. Whilst gene expression profiles (GEPs) have shown promise in identifying patients with LNM in early studies, these have not become a routine part of clinical practice. A limitation of these GEPs is that they are generic and so agnostic of other factors that could influence gene expression, such as tumour location and mismatch repair (MMR) status. In a retrospective translational study of 24 patients who underwent surgery for T1 CC, we demonstrate that both tumour location and MMR status have a significant impact on intratumoural gene expression. This impact was seen in patients with and without LNM. When compared to analyses of all patients, side-specific and MMR status-specific analyses revealed a higher number of differentially expressed genes with lower false discovery rates. Several interesting candidate genes for LNM were identified, including AHNAK, ATG12 and DMBT1. These findings demonstrate the influence of tumour location and MMR status on intratumoural gene expression in T1 CC and highlights the need to account for these factors when developing GEPs for clinical translation. - Source: PubMed
Publication date: 2026/05/14
Ebbehøj Anders LJørgensen Lars NChiranth DeepthiMelchior Linea CLitman ThomasKrarup Peter-MartinSmith Henry G - Proteasome subunit beta type-9 (PSMB9) is a catalytic subunit of the immunoproteasome and plays an essential role in antigen processing and MHC class I (MHC I)-restricted cellular immunity in mammals. However, the role of PSMB9 in fish antiviral immunity remains poorly understood. In this study, we cloned and characterized the PSMB9 homologue from orange-spotted grouper (Epinephelus coioides), designated EcPSMB9, and investigated its potential role in host defence against Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV). EcPSMB9 overexpression was consistently associated with reduced viral burden during both SGIV and RGNNV infection. In parallel, EcPSMB9 overexpression was accompanied by decreased GFP-LC3 puncta formation, lower LC3-II protein levels, and reduced expression of ATG5, ATG12, and ATG16, together with enhanced MHC I-associated and interferon-associated transcriptional activity, suggesting that EcPSMB9 may participate in antiviral defence through coordinated changes in proteostasis-related and antigen presentation-associated processes. Notably, structural modeling and co-immunoprecipitation analyses revealed an association between EcPSMB9 and the core immunoproteasome subunit EcPSMB8. Together, these findings suggest that EcPSMB9 is a conserved immunoproteasome subunit linked to antiviral responses in grouper and indicate that immunoproteasome subunit cooperation may be relevant to teleost antiviral immunity. - Source: PubMed
Publication date: 2026/05/12
Chen JinpengHe XinLi ShenHe YuhuiWei ShinaSun YunQin QiweiYang Min - Ubiquitin and ubiquitin-like proteins (UBLs) have emerged as critical regulators of protein homeostasis and cellular signaling, processes that are increasingly recognized as central to the pathogenesis of Alzheimer's disease (AD). This review explores the expanding roles of UBL modifiers, including SUMO, NEDD8, ISG15, UFM1, and ATG8/ATG12, in the development and progression of AD. We discuss how these post-translational modifications influence key pathological features of AD such as amyloid-beta accumulation and neurofibrillary tangles formation, as well as their impact on neuronal function, proteostasis, and neuroinflammation. Recent advances in our understanding of the enzymatic machinery mediating these modifications, and the interplay between different UBL proteins, offer new insights into the molecular mechanisms underlying AD. Furthermore, we highlight emerging therapeutic strategies targeting UBL pathways, which may provide novel avenues for intervention in AD. By integrating current findings, this review underscores the significance of UBL proteins in AD and identifies future directions for research aimed at unraveling their complex roles in neurodegeneration. - Source: PubMed
Publication date: 2026/05/08
Yan TingxiangVaquer JustineSpringer WolfdieterFiesel Fabienne C - Midbrain dopamine (mDA) neurons play a wide range of brain functions, but the molecular mechanisms driving the formation of mDA circuits remain largely unknown. Here, we show that autophagy, the main cellular recycling pathway, is present in the growth cones of developing mDA neurons, and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth and guidance, we knocked out essential autophagy genes (Atg12, Atg5) specifically in mDA neurons in mice of either sex. Autophagy-deficient mDA axons exhibit axonal swellings and reduced branching both and in vivo. Strikingly, deletion of autophagy-related genes completely blunted the response of mDA neurons to both chemorepulsive and chemoattractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neuron development by orchestrating axonal growth and guidance. Midbrain dopaminergic neurons form circuits essential for movement, motivation, and cognition, yet the intracellular mechanisms controlling their axon growth and guidance remain poorly understood. Here we show that autophagy, a major cellular recycling pathway, operates locally in dopaminergic growth cones and is dynamically regulated by guidance cues. Using neuron-specific deletion of core autophagy genes, we demonstrate that autophagy is required for proper axonal morphology, branching, and responsiveness to both chemoattractive and chemorepulsive signals. These findings identify autophagy as a key regulator of dopaminergic circuit formation and reveal a previously unrecognized mechanism linking intracellular degradation pathways to axon guidance during brain development. - Source: PubMed
Publication date: 2026/05/07
Schaan Profes MarcosGora CharlesLavoie-Cardinal FlavieSaghatelyan ArmenLévesque Martin