Світова економічна криза 2007–2008 років і потрясіння, що охо-
пили одночасно секторальні ринки кредитування, страхування, нерухомості та цінних паперів, продемонстрували, що системні ризики
підтримки фінансової стабільності не були належним чином оцінені
регуляторами

Avi Ashkenazi (30123)

Corey E. Bakalarski (2087389)

Daisy Bustos (2087377)

Donald S. Kirkpatrick (212573)

Jennie R. Lill (212568)

Kebing Yu (128199)

Qui T. Phung (2087386)

Robert Pitti (2087392)

Suchit Jhunjhunwala (2087380)

Veronica
G. Anania (1310877)

Victoria
C. Pham (2087395)

William
F. Forrest (2087383)

Proteolysis is a key regulatory event that controls intracellular
and extracellular signaling through irreversible changes in a protein’s
structure that greatly alters its function. Here we describe a platform
for profiling caspase substrates which encompasses two highly complementary
proteomic techniquesthe first is a differential gel based
approach termed Global Analyzer of SILAC-derived Substrates of Proteolysis
(GASSP) and the second involves affinity enrichment of peptides containing
a C-terminal aspartic acid residue. In combination, these techniques
have enabled the profiling of a large cellular pool of apoptotic-mediated
proteolytic events across a wide dynamic range. By applying this integrated
proteomic work flow to analyze proteolytic events resulting from the
induction of intrinsic apoptosis in Jurkat cells via etoposide treatment,
3346 proteins were quantified, of which 360 proteins were identified
as etoposide-induced proteolytic substrates, including 160 previously
assigned caspase substrates. In addition to global profiling, a targeted
approach using BAX HCT116 isogenic cell lines was utilized to dissect
pre- and post-mitochondrial extrinsic apoptotic cleavage events. By
employing apoptotic activation with a pro-apoptotic receptor agonist
(PARA), a limited set of apoptotic substrates including known caspase
substrates such as BH3 interacting-domain death agonist (BID) and
Poly (ADP-ribose) polymerase (PARP)-1, and novel substrates such as
Basic Transcription Factor 3, TRK-fused gene protein (TFG), and p62/Sequestosome
were also identified

The Francis Crick Institute

Complementary Proteomic
Tools for the Dissection of Apoptotic Proteolysis Events

https://figshare.com/articles/Complementary_Proteomic_Tools_for_the_Dissection_of_Apoptotic_Proteolysis_Events/2525932