Page 240 - Hematology_ Basic Principles and Practice ( PDFDrive )

192 Part II Cellular Basis of Hematology

BID BIM BAD NOXA PUMA BIK BMF HRK BNIP3
BH3-only
Proteins

Activators Sensitizers

MCL-1 BCL-X BCL-2 BAX BAK BOK
L

Multidomain
proteins

Antiapoptotic Proapoptotic

Gateway
organelles

Mitochondrion Endoplasmic reticulum

Cytochrome c release Calcium release

Apoptosome
Downstream formation
elements Caspase-3
activation

DEATH
Fig. 18.7 SCHEMATIC REPRESENTATION OF THE INTRINSIC APOPTOTIC PATHWAY IN
WHICH A BH3-ONLY MOLECULE SERVE AS UPSTREAM SENTINELS THAT SELECTIVELY
RESPOND TO SPECIFIC DEATH SIGNALS. BH3-only molecules ultimately regulate BAX and BAK
activation directly or indirectly. This process is in turn inhibited by antiapoptotic BCL-2 family members.
BAX and BAK serve as gateways to apoptosis, regulating both cytochrome c release from the mitochondria
2+
and Ca release from the endoplasmic reticulum (ER). See Fig. 18.6 for definition of abbreviations.