Ask about this productRelated genes to: DDI1 Blocking Peptide
- Gene:
- DDI1 NIH gene
- Name:
- DNA damage inducible 1 homolog 1
- Previous symbol:
- -
- Synonyms:
- FLJ36017
- Chromosome:
- 11q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-11-14
- Date modifiied:
- 2015-11-16
Related products to: DDI1 Blocking Peptide
Related articles to: DDI1 Blocking Peptide
- Polyubiquitin chains, linked via K48 or K63 of ubiquitin, direct membrane proteins in the secretory system to distinct degradative fates. However, it's unclear whether these linkage isomers are functionally interchangeable. Here we show that for post-endoplasmic reticulum (ER) proteins, K63-linked polyubiquitination induces sorting into multivesicular bodies (MVBs) and lysosomal degradation. In contrast, K48-linked polyubiquitination induces shearing from the membrane and proteasomal degradation. This process involves two ubiquitin-dependent proteases: Ddi1, a conserved cytosolic ubiquilin that generates fragments from soluble and membrane proteins, and Rbd2, an intramembrane rhomboid protease that produces lumenal fragments from membrane proteins at Golgi/endosomes and the vacuolar membrane. Ddi1's catalytic core, the HDD-RVP domain, is sufficient for ubiquitin-dependent proteolysis. It binds ubiquitin directly and its activity is enhanced by auxiliary ubiquitin binding domains: an atypical UBL domain and a UBA domain. These findings demonstrate that polyubiquitin chains linked by different residues encode distinct degradative fates for post-ER proteins, and reveal two proteases that target ubiquitinated integral membrane proteins in a process we call CUT-UP (Cleavage of Ubiquitinated Targets by Ubiquitin-dependent Proteases). - Source: PubMed
Publication date: 2026/01/13
Minard Annabel YWinistorfer StanleyYu LipingPiper Robert C - Oxidative stress is a major microbicidal mechanism of phagocytes causing molecular damages, including DNA-protein crosslinks (DPCs), toxic DNA lesions that can lead to genomic instability. DPC repair depends on Wss1 and Ddi1 proteases, so they may be critical for fungal survival in hosts, yet their roles have not been fully elucidated. In this study, the roles of Wss1 and Ddi1 under oxidative stress were examined in the model yeast Saccharomyces cerevisiae and Candida albicans, an important human fungal pathogen. Direct measurements of DPCs using SDS/KCl precipitation showed that oxidative stress inducers, including hydrogen peroxide, sodium hypochlorite, menadione and plumbagin, increased DPC levels in a dose-dependent manner in both species. S. cerevisiae and C. albicans lacking Wss1 and Ddi1 are hypersensitive to oxidative stress inducers. Complementation assays demonstrated that catalytic activity of CaWss1 is essential, while the interactions with Cdc48 and SUMO are important but not absolutely required. Importantly, CaWss1 and CaDdi1 play partially redundant roles for resistance to macrophage killing, with CaWss1 being more dominant. In conclusion, Wss1 and Ddi1 in both S. cerevisiae and C. albicans are required for survival under oxidative stress, and this may be critical for C. albicans to evade phagocytic killing and establish an infection. - Source: PubMed
Publication date: 2025/07/23
Sukted JuthamasJunsuntonpass ArnonchaiHomchan AimornMongkolsuk SkornPakotiprapha DanayaMatangkasombut Oranart - Although an established correlation exists between tumor cell proliferation and elevated polyamine levels, research on polyamine metabolism in osteosarcoma (OS) remains limited. This study aimed to identify polyamine metabolism-related genes (PMRGs) associated with OS prognosis and develop a prognostic model, thereby offering novel insights into targeted therapies for patients with OS. - Source: PubMed
Publication date: 2025/05/18
Qiu ShuoTan ChenCheng DongdongYang Qingcheng - Since their domestication, domestic sheep (Ovis aries) have been culturally and economically significant farming animals worldwide. Fat-tailed sheep serve as a unique genetic resource for understanding adipogenesis and adaptive evolution in livestock. - Source: PubMed
Publication date: 2025/05/06
Jin MeilinLiu GangLiu EnminWang LizhongJiang YuZheng ZhuqingLu JianLu ZengkuiMa YoujiLiu YongbinQuan KaiJin HaiJiang XunpingFei XiaojuanLi TaotaoCao JiaxueYuan ZehuDu LixinWang HuihuaWei Caihong - Human malaria remains a global health challenge, with Plasmodium falciparum responsible for the most severe cases. Despite global efforts, eradicating malaria has proven difficult, mainly because of the rise in drug resistance, particularly against artemisinin and its derivatives. One possible cause of this resistance is the activation of the unfolded protein response (UPR), which helps maintain cellular balance under stress. In P. falciparum, the UPR operates through the ubiquitin-proteasome system (UPS), which involves proteins such as Dsk2, Rad23, and Ddi1. Among these, Plasmodium falciparum DNA-damage-inducible protein 1 (PfDdi1) plays a crucial role in DNA repair and is present throughout the parasite life cycle, making it an attractive drug target. However, there is limited research on PfDdi1 as a therapeutic target. Recent in vitro studies have indicated that artemisinin (ART) and dihydroartemisinin (DHA) inhibit PfDdi1 activity. Building on this, we investigated whether ART and its derivatives could serve as inhibitors of PfDdi1 using computational modeling. Our study included clinically relevant ART derivatives such as artemether (ARM), arteether (AET), artemiside (AMD), and artesunate (ATS). All these compounds showed strong binding to PfDdi1, with free binding energies ranging from -20.75 kcal/mol for AET to -34.24 kcal/mol for ATS. ARM increased PfDdi1's structural rigidity and hydrophobic stability, whereas AMD improved its kinetic stability, resulting in the least residue motion. Unlike AET and AMD, the other ligands destabilize the PfDdi1 structure. Importantly, three key binding regions-Loop 1 (GLN 266 - ILE 269), Loop 2 (ILE 323 - TYR 326), and Loop 3 (ALA 292 - GLY 294)-were identified as potential targets for new antimalarial drugs against PfDdi1. This study highlights the potential of ART derivatives as PfDdi1 inhibitors, paving the way for further experimental validation. - Source: PubMed
Publication date: 2025/03/20
Oduro-Kwateng ErnestKehinde Ibrahim OluwatobiAli MusabKasumbwe KabangeMzozoyana VuyisaParinandi Narasimham LSoliman Mahmoud E S