ArticleCell death & disease2021
Cdk5rap3 is essential for intestinal Paneth cell development and maintenance.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Paneth cell-derived Notch ligands DLL1 and DLL4 are crucial for intestinal crypt base stem cells.bioRxiv : the preprint server for biology · 2026Article
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- A UFMylation-COPII axis orchestrates lipid transport in intestinal enterocytes and regulates systemic lipid balance.Molecular metabolism · 2026Article
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- A severe neurodevelopmental syndrome linked to a South Asian founder variant in the UFMylation adaptor CDK5RAP3.Acta neuropathologica · 2026Article
- Analysis of RNA Expression Specificity and Commonality in Commonly Used Tool Cells and Multiple Tissues of Pigs.Biomolecules · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- CDK5RAP3 Regulates Testosterone Production in Mouse Leydig Cells.International journal of molecular sciences · 2026Article
- Endoplasmic reticulum autophagy in inflammatory diseases.Frontiers in immunology · 2026Review
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- Nuclear translocation of CDK5RAP3 regulated by NXF3 promotes the progression of gastric cancer.Cellular and molecular life sciences : CMLS · 2025Article
- TSPAN6 reinforces the malignant progression of glioblastoma via interacting with CDK5RAP3 and regulating STAT3 signaling pathway.International journal of biological sciences · 2024Article
- Review
- Loss of Ufl1/Ufbp1 in hepatocytes promotes liver pathological damage and carcinogenesis through activating mTOR signaling.Journal of experimental & clinical cancer research : CR · 2023Article
- Regional epithelial cell diversity in the small intestine of pigs.Journal of animal science · 2023Article
- Paneth cell development in the neonatal gut: pathway regulation, development, and relevance to necrotizing enterocolitis.Frontiers in cell and developmental biology · 2023Review
- UFL1, a UFMylation E3 ligase, plays a crucial role in multiple cellular stress responses.Frontiers in endocrinology · 2023Review
- CDK5RAP3, an essential regulator of checkpoint, interacts with RPL26 and maintains the stability of cell growth.Cell proliferation · 2022Article
- C53 Interacting with UFM1-Protein Ligase 1 Regulates Microtubule Nucleation in Response to ER Stress.Cells · 2022Article
- Effect of the Microbiome on Intestinal Innate Immune Development in Early Life and the Potential Strategy of Early Intervention.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Intestinal Paneth cells are professional exocrine cells that play crucial roles in maintenance of homeostatic microbiome, modulation of mucosal immunity, and support for stem cell self-renewal. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Cdk5 activator binding protein Cdk5rap3 (also known as C53 and LZAP) was originally identified as a binding protein of Cdk5 activator p35. Although previous studies have indicated its involvement in a wide range of signaling pathways, the physiological function of Cdk5rap3 remains largely undefined. In this study, we found that Cdk5rap3 deficiency resulted in very early embryonic lethality, indicating its indispensable role in embryogenesis. To further investigate its function in the adult tissues and organs, we generated intestinal epithelial cell (IEC)-specific knockout mouse model to examine its role in intestinal development and tissue homeostasis. IEC-specific deletion of Cdk5rap3 led to nearly complete loss of Paneth cells and increased susceptibility to experimentally induced colitis. Interestingly, Cdk5rap3 deficiency resulted in downregulation of key transcription factors Gfi1 and Sox9, indicating its crucial role in Paneth cell fate specification. Furthermore, Cdk5rap3 is highly expressed in mature Paneth cells. Paneth cell-specific knockout of Cdk5rap3 caused partial loss of Paneth cells, while inducible acute deletion of Cdk5rap3 resulted in disassembly of the rough endoplasmic reticulum (RER) and abnormal zymogen granules in the mature Paneth cells, as well as loss of Paneth cells. Together, our results provide definitive evidence for the essential role of Cdk5rap3 in Paneth cell development and maintenance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.