HRK (harakiri, BCL2 interacting protein (contains only BH3 domain))

Abstract

HRK / Dp5 / Bid3 is a BH3-only member of the Bcl-2 family of apoptosis regulators. Bcl-2 family proteins regulate the mitochondrial (intrinsic) pathway of apoptosis by regulating mitochondrial outer membrane permeability. Interactions between the pro- and anti-apoptotic members of the Bcl-2 family determine the fate of cells in response to signals that induce apoptosis. BH3-only proteins are activated in response to a variety of signals including survival factor withdrawal, DNA damage, ER stress and oxidative stress. HRK expression increases following Nerve Growth Factor (NGF) withdrawal in sympathetic neurons, neuronally differentiated PC12 cells and dorsal root ganglion (DRG) neurons, KCl deprivation in cerebellar granule neurons, beta amyloid treatment in cortical neurons and following axotomy of motor neurons in vivo. Experiments with HRK-/- knockout mice have shown that HRK is not essential for normal embryonic development but does contribute to the death of DRG neurons following NGF deprivation in vitro and the death of motoneurons in vivo following hypoglossal nerve transection.