Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP
The new and growing family of interleukin-1β-converting enzyme (ICE) cysteine proteases are now recognised to be major effectors of cellular death by apoptosis. Like other members of this family, the CPP32/Yama proform is activated by processing to its active heterodimeric enzyme or apopain when it...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
1996
|
| Subjects: |
| _version_ | 1797050842140901376 |
|---|---|
| author | An, S Knox, K |
| author2 | Federation of European Biochemical Societies |
| author_facet | Federation of European Biochemical Societies An, S Knox, K |
| author_sort | An, S |
| collection | OXFORD |
| description | The new and growing family of interleukin-1β-converting enzyme (ICE) cysteine proteases are now recognised to be major effectors of cellular death by apoptosis. Like other members of this family, the CPP32/Yama proform is activated by processing to its active heterodimeric enzyme or apopain when it likely contributes to the process of apoptosis by cleaving poly(ADP-ribose) polymerase (PARP) and thereby inhibiting much of its DNA repair activity. Apoptosis plays a fundamental role in the regulation of the immune system where it is involved in the selection of both T and B lymphocytes bearing antigen receptor (AgR) for non-self. Cells of the Ramos Epstein-Barr virus (EBV)-genome-negative Burkitt lymphoma (BL) B cell line (Ramos-BL) can be triggered into growth arrest and apoptosis by treating with the calcium ionophore ionomycin or by crosslinking their surface AgR with antibodies directed against immunoglobulin (Ig)M (anti-IgM). Ionomycin- and AgR-triggered growth arrest and apoptosis are arrested by signals transduced through the surface CD40 of Ramos-BL B cells. Both ionomycin and anti-IgM trigger activation of CPP32 and cleavage of PARP prior to the onset of apoptosis; this process is abrogated by treatment with anti-CD40 and is independent of Bcl-2 expression. A tripeptide inhibitor of ICE family cysteine proteases, Z-Val-Ala-Asp-fluoromethylketone (zVAD-<em>fmk</em>) inhibits ionomycin- and AgR-triggered CPP32 activation, PARP cleavage and apoptosis, but not growth arrest, in Ramos-BL B cells. Thus, in this report we demonstrate that in a physiological system, activation of endogenous members of the ICE family, including CPP32, and cleavage of the death substrate PARP act as major effectors of apoptotic death. |
| first_indexed | 2024-03-06T18:11:11Z |
| format | Journal article |
| id | oxford-uuid:03124e78-2aba-40b5-a72e-dbb4a54ea487 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:11:11Z |
| publishDate | 1996 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:03124e78-2aba-40b5-a72e-dbb4a54ea4872022-03-26T08:44:06ZLigation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARPJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:03124e78-2aba-40b5-a72e-dbb4a54ea487BiochemistryEnglishOxford University Research Archive - ValetElsevier1996An, SKnox, KFederation of European Biochemical SocietiesThe new and growing family of interleukin-1β-converting enzyme (ICE) cysteine proteases are now recognised to be major effectors of cellular death by apoptosis. Like other members of this family, the CPP32/Yama proform is activated by processing to its active heterodimeric enzyme or apopain when it likely contributes to the process of apoptosis by cleaving poly(ADP-ribose) polymerase (PARP) and thereby inhibiting much of its DNA repair activity. Apoptosis plays a fundamental role in the regulation of the immune system where it is involved in the selection of both T and B lymphocytes bearing antigen receptor (AgR) for non-self. Cells of the Ramos Epstein-Barr virus (EBV)-genome-negative Burkitt lymphoma (BL) B cell line (Ramos-BL) can be triggered into growth arrest and apoptosis by treating with the calcium ionophore ionomycin or by crosslinking their surface AgR with antibodies directed against immunoglobulin (Ig)M (anti-IgM). Ionomycin- and AgR-triggered growth arrest and apoptosis are arrested by signals transduced through the surface CD40 of Ramos-BL B cells. Both ionomycin and anti-IgM trigger activation of CPP32 and cleavage of PARP prior to the onset of apoptosis; this process is abrogated by treatment with anti-CD40 and is independent of Bcl-2 expression. A tripeptide inhibitor of ICE family cysteine proteases, Z-Val-Ala-Asp-fluoromethylketone (zVAD-<em>fmk</em>) inhibits ionomycin- and AgR-triggered CPP32 activation, PARP cleavage and apoptosis, but not growth arrest, in Ramos-BL B cells. Thus, in this report we demonstrate that in a physiological system, activation of endogenous members of the ICE family, including CPP32, and cleavage of the death substrate PARP act as major effectors of apoptotic death. |
| spellingShingle | Biochemistry An, S Knox, K Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP |
| title | Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP |
| title_full | Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP |
| title_fullStr | Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP |
| title_full_unstemmed | Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP |
| title_short | Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP |
| title_sort | ligation of cd40 rescues ramos burkitt lymphoma b cells from calcium ionophore and antigen receptor triggered apoptosis by inhibiting activation of the cysteine protease cpp32 yama and cleavage of its substrate parp |
| topic | Biochemistry |
| work_keys_str_mv | AT ans ligationofcd40rescuesramosburkittlymphomabcellsfromcalciumionophoreandantigenreceptortriggeredapoptosisbyinhibitingactivationofthecysteineproteasecpp32yamaandcleavageofitssubstrateparp AT knoxk ligationofcd40rescuesramosburkittlymphomabcellsfromcalciumionophoreandantigenreceptortriggeredapoptosisbyinhibitingactivationofthecysteineproteasecpp32yamaandcleavageofitssubstrateparp |