Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21
- PMID: 10022130
- DOI: 10.1038/sj.onc.1202409
Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21
Abstract
The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery. Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site. Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.
Similar articles
-
Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP.Oncogene. 1998 Aug 27;17(8):931-9. doi: 10.1038/sj.onc.1202021. Oncogene. 1998. PMID: 9747872
-
Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death.Oncogene. 2000 Mar 2;19(10):1346-53. doi: 10.1038/sj.onc.1203429. Oncogene. 2000. PMID: 10713676
-
Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A.Cell Death Differ. 2000 Aug;7(8):721-8. doi: 10.1038/sj.cdd.4400706. Cell Death Differ. 2000. PMID: 10918446
-
Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis.Oncogene. 1999 Feb 4;18(5):1131-8. doi: 10.1038/sj.onc.1202426. Oncogene. 1999. PMID: 10022118
-
ILP-2: A New Bane and Therapeutic Target for Human Cancers.Front Oncol. 2022 Jun 23;12:922596. doi: 10.3389/fonc.2022.922596. eCollection 2022. Front Oncol. 2022. PMID: 35814477 Free PMC article. Review.
Cited by
-
Somatic cell type specific gene transfer reveals a tumor-promoting function for p21(Waf1/Cip1).EMBO J. 2007 Nov 14;26(22):4683-93. doi: 10.1038/sj.emboj.7601886. Epub 2007 Oct 18. EMBO J. 2007. PMID: 17948060 Free PMC article.
-
Phosphatidylinositol 3-Akt-kinase-dependent phosphorylation of p21(Waf1/Cip1) as a novel mechanism of neuroprotection by glucocorticoids.J Neurosci. 2007 Apr 25;27(17):4562-71. doi: 10.1523/JNEUROSCI.5110-06.2007. J Neurosci. 2007. PMID: 17460069 Free PMC article.
-
Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotection.J Neurosci. 2008 Jan 2;28(1):163-76. doi: 10.1523/JNEUROSCI.3200-07.2008. J Neurosci. 2008. PMID: 18171934 Free PMC article.
-
Romidepsin hepatocellular carcinoma suppression in mice is associated with deregulated gene expression of bone morphogenetic protein and Notch signaling pathway components.Mol Biol Rep. 2021 Jan;48(1):551-562. doi: 10.1007/s11033-020-06089-9. Epub 2021 Jan 3. Mol Biol Rep. 2021. PMID: 33393006
-
Protective roles of cytoplasmic p21Cip1 /Waf1 in senolysis and ferroptosis of lung cancer cells.Cell Prolif. 2022 Dec;55(12):e13326. doi: 10.1111/cpr.13326. Epub 2022 Aug 30. Cell Prolif. 2022. PMID: 36054146 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
