Ask about this productRelated genes to: TOM1 Blocking Peptide
- Gene:
- TOM1 NIH gene
- Name:
- target of myb1 membrane trafficking protein
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 22q12.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-10-14
- Date modifiied:
- 2016-10-05
Related products to: TOM1 Blocking Peptide
Related articles to: TOM1 Blocking Peptide
- Autophagy plays a critical role in viral replication and the regulation of host immune responses. Although the TOM1-TOLLIP complex has been implicated in immune signaling, cargo trafficking, and endocytosis, its role in viral replication has not been defined. Here, we demonstrate that the SARS-CoV-2 main protease (NSP5) cleaves TOM1 at residue Q354 through its protease activity. This cleavage is also observed with the main proteases of SARS-CoV and MERS-CoV. Importantly, TOM1 overexpression suppresses SARS-CoV-2 replication in HEK293T-hACE2 and Vero cells, while TOM1 knockout via CRISPR-Cas9 significantly enhances viral propagation, indicating that TOM1 functions as a novel restriction factor against SARS-CoV-2 infection. Moreover, various TOM1 orthologs from diverse species, including cattle, bats, monkeys, mice, and ducks, show similar restriction to SARS-CoV-2, but they all are antagonized by NSP5 cleavage. Mechanistically, we found that TOM1 recruits the autophagy receptor TOLLIP to target SARS-CoV-2 envelope (E) protein for autophagic degradation, thereby limiting viral replication. These findings highlight the importance of the TOM1-TOLLIP complex in host defense and discover that SARS-CoV-2 exploits a conserved NSP5-mediated TOM1 cleavage mechanism to evade host antiviral defenses.IMPORTANCEViruses must overcome the body's natural defenses in order to replicate and spread. One important cellular defense mechanism is autophagy, a process that helps cells remove harmful proteins and pathogens. In this study, we discovered that a host protein called TOM1 acts as a restriction factor that helps limit the replication of SARS-CoV-2, the virus responsible for COVID-19. TOM1 works together with another protein, TOLLIP, to direct envelope proteins to the cell's degradation system, thereby reducing viral replication. However, SARS-CoV-2 has evolved a strategy to counter this defense. The viral main protease (NSP5) cleaves TOM1, disabling its antiviral activity. This mechanism is conserved among several coronaviruses, including SARS-CoV and MERS-CoV. Our findings reveal a previously unrecognized antiviral role of the TOM1-TOLLIP complex and demonstrate how coronaviruses evade this host defense, providing new insight into virus-host interactions and potential targets for antiviral therapies. - Source: PubMed
Publication date: 2026/06/12
Zhang QingxiangXin JingguoWang ChunleiZhang XueGao YuanGao WenyingZhang Wenyan - Intracellular signaling pathways are modulated by ubiquitin-dependent trafficking, in which specific plasma membrane receptors and cytosolic proteins are tagged, internalized, and degraded in the endolysosomal pathway. Target of Myb1 (TOM1) family proteins, including TOM1, TOM1-L1, and TOM1-L2 function as early adaptors within the ESCRT-0 machinery to recognize ubiquitinated cargo and coordinate its sorting. TOM1 proteins interact with ubiquitin and accessory proteins, such as TOLLIP, facilitating efficient cargo sequestration and endosomal maturation. These interactions are known to be modulated by pathogen-driven processes, such as Shigella flexneri-mediated phosphatidylinositol 5-phosphate accumulation, which can impair TOM1-dependent cargo trafficking. Beyond endosomal sorting, TOM1 contributes to autophagic flux by linking autophagosomes and endosomes through its interaction with the motor protein Myosin VI. Dysregulation of these pathways has been implicated in immune disorders, myocardial ischemia-reperfusion injury, and potentially tumorigenesis. In plants, TOM1-like proteins serve as functional ESCRT-0 analogs, mediating ubiquitin-dependent cargo sorting and integrating stress-responsive signaling. Recent studies have shed light on the modular organization of TOM1, revealing mechanisms of ubiquitin recognition, DXXLL motif function, and complex formation with adaptor proteins. Nonetheless, key questions remain regarding how TOM1 discriminates among ubiquitin linkages, interacts with distinct phosphoinositides under varying physiological conditions, and cooperates with TOLLIP during selective autophagy. Elucidating these mechanisms will advance our understanding of cellular transport and signaling and may reveal novel intervention targets for inflammatory and autoimmune diseases in humans as well as for improving drought tolerance and immune regulation in plants. - Source: PubMed
Publication date: 2026/05/26
Collins Megan VLång Heljä K MFinkielstein Carla VRyhänen Samppa JIkonen ElinaCapelluto Daniel G S - The advent of genome editing technologies such as CRISPR-Cas9 has revolutionized the development of disease-resistant crops, offering precision and efficiency in targeting specific genetic loci responsible for susceptibility. In this protocol, we harness the CRISPR-Cas9 system to disrupt key susceptibility genes in tomato, aiming to fortify resistance against tobamoviruses, particularly the aggressive tomato brown rugose fruit virus (ToBRFV). By systematically knocking out four TOM1 homologs, genes essential for tobamoviral replication, tomato lines with robust and heritable resistance can be developed while minimizing adverse developmental effects. The approach not only underscores the significance of basic research on host-pathogen interactions in modern crop protection but also lays the groundwork for sustainable, gene-driven resistance strategies in commercial tomato breeding. - Source: PubMed
Watanabe KikyoIshikawa MasayukiIshibashi Kazuhiro - Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease. As stress-responsive membraneless organelles, stress granules (SGs) are involved in modulating inflammatory suppression and promoting tumorigenesis, but their role in the pathogenesis of CAC remains unclear. This study reveals that SGs exhibit a stage-specific function during CAC progression, being protective in acute colitis but transitioning to a tumor-promoting role in the dysplasia-carcinoma sequence. We first demonstrate that, during acute colitis, fluctuating oxidative stress drives dynamic SGs assembly. However, despite persistently elevated oxidative stress from chronic colitis to dysplasia, SGs levels paradoxically decline. This decline is attributed to the upregulation of TOM1, a novel negative regulator that binds the NTF2L domain of the core SGs scaffold protein G3BP1 to promote SGs disassembly, thereby counteracting the oxidative stress-driven assembly. The consequent disassembly facilitates the nuclear translocation of the oncogenic transcription factor FUBP1, which in turn promotes c-Myc expression and thereby contributes to tumorigenesis. Our findings establish the regulation of SGs dynamics, particularly via TOM1 and G3BP1, as a promising therapeutic strategy for CAC. - Source: PubMed
Publication date: 2026/05/07
Wan ZiyuQian MeiruiYu JiawenShu TaiyuWang DanLiang XueChen RuoShi BoCui HongyongChen ZhinanJiang Jianli - There is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood. - Source: PubMed
Publication date: 2025/09/18
Yang JiaqiBernard LaurenChen JingshaSullivan Valerie KYu BingRhee Eugene PWelling Paul ARebholz Casey M