scholarly journals Activation of Initiator Caspases through a Stable Dimeric Intermediate

2002 ◽  
Vol 277 (52) ◽  
pp. 50761-50767 ◽  
Author(s):  
Min Chen ◽  
Aaron Orozco ◽  
David M. Spencer ◽  
Jin Wang
Keyword(s):  
Initiator Caspases ◽  
Dimeric Intermediate

Identification of a Dimeric Intermediate in the Unfolding Pathway for the Calcium-Binding Protein S100B

2008 ◽  
Vol 382 (4) ◽  
pp. 1075-1088 ◽  
Author(s):  
Gary S. Shaw ◽  
Nicole M. Marlatt ◽  
Peter L. Ferguson ◽  
Kathryn R. Barber ◽  
Stephen P. Bottomley
Keyword(s):  
Calcium Binding ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Dimeric Intermediate ◽  
Protein S100b

scholarly journals Comparing the folding landscapes of evolutionarily divergent procaspase-3

2022 ◽  
Author(s):  
Liqi Yao ◽  
Clay Clark
Keyword(s):  
Conformational Change ◽  
Common Ancestor ◽  
Folding Pathway ◽  
Free Energies ◽  
Folding Intermediates ◽  
Effector Caspases ◽  
The Common ◽  
Ph Dependent ◽  
Species Specific ◽  
Dimeric Intermediate

All caspases evolved from a common ancestor and subsequently developed into two general classes, inflammatory or apoptotic caspases. The caspase-hemoglobinase fold has been conserved throughout nearly one billion years of evolution and is utilized for both the monomeric and dimeric subfamilies of apoptotic caspases, called initiator and effector caspases, respectively. We compared the folding and assembly of procaspase-3b from zebrafish to that of human effector procaspases in order to examine the conservation of the folding landscape. Urea-induced equilibrium folding/unfolding of procaspase-3b showed a minimum three-state folding pathway, where the native dimer isomerizes to a partially folded dimeric intermediate, which then unfolds. A partially folded monomeric intermediate observed in the folding landscape of human procaspase-3 is not well-populated in zebrafish procaspase-3b. By comparing effector caspases from different species, we show that the effector procaspase dimer undergoes a pH-dependent conformational change, and that the conformational species in the folding landscape exhibit similar free energies. Together, the data show that the landscape for the caspase-hemoglobinase fold is conserved, yet it provides flexibility for species-specific stabilization or destabilization of folding intermediates resulting in changes in stability. The common pH-dependent conformational change in the native dimer, which yields an enzymatically inactive species, may provide an additional, albeit reversible, mechanism for controlling caspase activity in the cell.

scholarly journals Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Rajni Kumari ◽  
Ruhi S. Deshmukh ◽  
Sanjeev Das
Keyword(s):  
Histone H3 ◽  
Caspase 8 ◽  
Epigenetic Mechanisms ◽  
Lipid Levels ◽  
Malignant Phenotype ◽  
Atp Citrate Lyase ◽  
Intracellular Lipid ◽  
Citrate Lyase ◽  
Initiator Caspases ◽  
Close Homolog

Abstract Caspase-10 belongs to the class of initiator caspases and is a close homolog of caspase-8. However, the lack of caspase-10 in mice and limited substrate repertoire restricts the understanding of its physiological functions. Here, we report that ATP-citrate lyase (ACLY) is a caspase-10 substrate. Caspase-10 cleaves ACLY at the conserved Asp1026 site under conditions of altered metabolic homeostasis. Cleavage of ACLY abrogates its enzymatic activity and suppresses the generation of acetyl-CoA, which is critical for lipogenesis and histone acetylation. Thus, caspase-10-mediated ACLY cleavage results in reduced intracellular lipid levels and represses GCN5-mediated histone H3 and H4 acetylation. Furthermore, decline in GCN5 activity alters the epigenetic profile, resulting in downregulation of proliferative and metastatic genes. Thus caspase-10 suppresses ACLY-promoted malignant phenotype. These findings expand the substrate repertoire of caspase-10 and highlight its pivotal role in inhibiting tumorigenesis through metabolic and epigenetic mechanisms.

In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis

2005 ◽  
Vol 8 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Shine Tu ◽  
Gavin P. McStay ◽  
Louis-Martin Boucher ◽  
Tak Mak ◽  
Helen M. Beere ◽  
...  
Keyword(s):  
Heat Shock ◽  
Initiator Caspases ◽  
Caspase 2 ◽  
Induced Apoptosis

Evidence of a Thermal Unfolding Dimeric Intermediate for the Escherichia coli Histone-like HU Proteins: Thermodynamics and Structure

2003 ◽  
Vol 331 (1) ◽  
pp. 101-121 ◽  
Author(s):  
Jean Ramstein ◽  
Nadège Hervouet ◽  
Franck Coste ◽  
Charles Zelwer ◽  
Jacques Oberto ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Thermal Unfolding ◽  
Hu Proteins ◽  
Dimeric Intermediate
Sign in / Sign up

Export Citation Format

Share Document