ArticleOncogene2000
Caspase-dependent cleavage and inactivation of the Vav1 proto-oncogene product during apoptosis prevents IL-2 transcription.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Vav1 mutations identified in human cancers give rise to different oncogenic phenotypes.Oncogenesis · 2018Article
- Vav family exchange factors: an integrated regulatory and functional view.Small GTPases · 2014Review
- Dynamin 2 potentiates invasive migration of pancreatic tumor cells through stabilization of the Rac1 GEF Vav1.Developmental cell · 2013Article
- The distinct role of guanine nucleotide exchange factor Vav1 in Bcl-2 transcription and apoptosis inhibition in Jurkat leukemia T cells.Acta pharmacologica Sinica · 2011Article
- hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation.International immunology · 2009Article
- Targeted cleavage of signaling proteins by caspase 3 inhibits T cell receptor signaling in anergic T cells.Immunity · 2008Article
- FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies.The EMBO journal · 2007Article
- Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity.Genes & development · 2003Article
- Many cuts to ruin: a comprehensive update of caspase substrates.Cell death and differentiation · 2003Review
- Caspase-dependent cleavage of the hematopoietic specific adaptor protein Gads alters signalling from the T cell receptor.Oncogene · 2001Article
- Vav family proteins couple to diverse cell surface receptors.Molecular and cellular biology · 2000Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here we identify the hematopoietic proto-oncogene Vav1 as a caspase substrate during apoptosis in lymphoid cells. Cleavage of Vav1 is prevented by the caspase inhibitors zDEVD and zVAD as well as by expression of CrmA. Vav1 is cleaved in vivo at the evolutionary conserved caspase consensus cleavage site DLYD161C, generating the carboxy-terminal cleavage product Vav1p76 of intermediate stability. In vitro caspase assays reveal cleavage of Vav1 at position 161 either by apoptotic cell lysates or by recombinant caspase-3. Mutation of Asp 161 to Ala leads to the usage of the adjacent alternative cleavage sequence DQID150D. Mutation of both cleavage sites at position 150 and 161 protects Vav1 from caspase-mediated proteolysis in vitro and in vivo. The cleavage product Vav1p76 is capable of activating JNK in T-cells, but fails to induce the phosphorylation of p38/HOG1. Vav1p76 displays a diminished capacity to activate the transcription factors NF-AT, AP-1 and NF-kappaB, and thus completely fails to activate IL-2 transcription. Since Vav1 is essential for IL-2 production and plays a central role for cytoskeletal reorganization, its proteolytic inactivation during apoptosis affects multiple downstream targets.
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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.