p97 (also called VCP or Cdc48p) and E3 ubiquitin ligases are the key players in retrotranslocation and ubiquitination of substrates in the endoplasmic reticulum-associated degradation (ERAD) pathways. Although their biochemical properties have been well studied, their cellular functions in development have not been revealed. Here, we investigate cellular functions of p97 and E3 ubiquitin ligases in Caenorhabditis elegans as a model organism. We found that C. elegans possesses three E3 ubiquitin ligases (named as HRD-1, HRDL-1 and MARC-6) like mammals, and that their simultaneous depletion caused extremely delayed growth. By monitoring the expression of an ER chaperone gene, it was revealed that p97 and HRD-1 play essential roles in unfolded protein response (UPR) and ERAD pathways. We further found that HRD-1 functions in concert with BiP, and that two BiP paralogues are functionally diversified. HRD-1 and BiP(HSP-3) play important roles in the developmental growth and function of intestinal cells, while HRD-1 and BiP(HSP-4) in the gonad formation. We propose that E3 ubiquitin ligases function in concert with a specific partner chaperone.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1365-2443.2007.01108.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NUMB alternative splicing and isoform specific functions in development and disease.
J Biol Chem
January 2025
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address:
The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.
View Article and Find Full Text PDFRecombinant Antibodies Inhibit Enzymatic Activity of the E3 Ubiquitin Ligase CHIP via Multiple Mechanisms.
J Biol Chem
January 2025
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:
Carboxyl-terminus of Hsp70-Interacting Protein (CHIP) is an E3 ubiquitin ligase that marks misfolded substrates for degradation. Hyper-activation of CHIP has been implicated in multiple diseases, including cystic fibrosis and cancer, suggesting that it may be a potential drug target. However, there are few tools available for exploring this possibility.
View Article and Find Full Text PDFA novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.
Pharm Biol
December 2025
The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China.
Context: The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.
Objective: To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.
Emerging Roles of TRIM56 in Antiviral Innate Immunity.
Viruses
January 2025
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
The tripartite-motif protein 56 (TRIM56) is a RING-type E3 ubiquitin ligase whose functions were recently beginning to be unveiled. While the physiological role(s) of TRIM56 remains unclear, emerging evidence suggests this protein participates in host innate defense mechanisms that guard against viral infections. Interestingly, TRIM56 has been shown to pose a barrier to viruses of distinct families by utilizing its different domains.
View Article and Find Full Text PDFGlobal Transcriptomic Analysis of Inbred Lines Reveal Candidate Genes for Response to Maize Lethal Necrosis.
Plants (Basel)
January 2025
Corteva Agriscience, 7000 NW 62nd Ave, Johnston, IA 50131, USA.
Maize lethal necrosis (MLN) is a significant threat to food security in Sub-Saharan Africa (SSA), with limited commercial inbred lines displaying tolerance. This study analyzed the transcriptomes of four commercially used maize inbred lines and a non-adapted inbred line, all with varying response levels to MLN. RNA-Seq revealed differentially expressed genes in response to infection by maize chlorotic mottle virus (MCMV) and sugarcane mosaic virus (SCMV), the causative agents of MLN.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!