Caspase-3 triggers a TPCK-sensitive protease pathway leading to degradation of the BH3-only protein puma

Apoptosis : an International Journal on Programmed Cell Death
Abbas HadjiAimé Vazquez

Abstract

The protein Puma (p53-upregulated modulator of apoptosis) belongs to the BH3-only group of the Bcl-2 family and is a major regulator of apoptosis. Although the transcriptional regulation of Puma is clearly established, little is known about the regulation of its expression at the protein levels. We show here that various signals--including the cytokine TGFβ, the death effector TRAIL or chemical drugs such as anisomycin--downregulate Puma protein levels via a novel pathway based on the sequential activation of caspase-3 and a protease inhibited by the serpase inhibitor N-tosyl-L-phenylalanine chloromethyl ketone. This pathway is specific for Puma because (1) the levels of other BH3-only proteins, such as Bim and Noxa were not modified by these stimuli and (2) this caspase-mediated degradation was dependent on both the BH3 and C-terminal domains of Puma. Our data also show that Puma is regulated during the caspase-3-dependent differentiation of murine embryonic stem cells and suggest that this pathway may be relevant and important during caspase-mediated cell differentiation not associated with apoptosis.

References

Dec 22, 1999·The Journal of Experimental Medicine·N J KennedyR C Budd
Sep 20, 2000·Leukemia·D E Johnson
Feb 24, 2001·The Journal of Experimental Medicine·Y ZermatiO Hermine
Jul 21, 2001·Molecular Cell·J YuB Vogelstein
Jul 21, 2001·Molecular Cell·K Nakano, K H Vousden
Apr 20, 2002·The Journal of Biological Chemistry·Hammou OubrahimEarl R Stadtman
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Pasan FernandoLynn A Megeney
Nov 14, 2002·Cell Cycle·Jerzy GrabarekZbigniew Darzynkiewicz
Feb 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jian YuLin Zhang
Oct 31, 2003·Cancer Cell·John R JeffersGerard P Zambetti
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shahul MouhamadAimé Vazquez
Sep 29, 2004·The Journal of Experimental Medicine·Silke F FischerGeorg Häcker
Nov 13, 2004·Cell Cycle·Malcolm A KingZbigniew Darzynkiewicz
Dec 16, 2004·The Journal of Clinical Investigation·Masako MiuraSongtao Shi
Mar 23, 2005·Oncogene·Laurence Besnault-MascardAimé Vazquez
Aug 5, 2005·Oncogene·Sophie LaunayCarmen Garrido
Aug 29, 2006·The American Journal of Pathology·Thomas Q NhanStephen M Schwartz
Nov 10, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pasan Fernando, Lynn A Megeney
Nov 23, 2006·Nature Cell Biology·Hyungjin KimEmily H-Y Cheng
Jun 5, 2008·Cell Stem Cell·Viktor JanzenDavid T Scadden
Jun 5, 2008·Cell Stem Cell·Jun FujitaThomas P Zwaka
Oct 7, 2008·Journal of Molecular Biology·Bernard A CallusDavid L Vaux
Oct 8, 2008·The Journal of Experimental Medicine·Elizabeth Yee-Wai ChoyDong-Yan Jin
Dec 17, 2008·Cell Death and Differentiation·A M JabbourP G Ekert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis