Gennady Ermak

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Reactive oxygen and nitrogen species can be used as a messengers in normal cell functions. However, at oxidative stress levels they can disrupt normal physiological pathways and cause cell death. Such a switch is largely mediated through Ca(2+) signaling. Oxidative stress causes Ca(2+) influx into the cytoplasm from the extracellular environment and from(More)
The DSCR1 (Adapt78) gene was independently discovered as a resident of the "Down syndrome candidate region"and as an "adaptive response"shock or stress gene that is transiently induced during oxidative stress. Recently the DSCR1 (Adapt78) gene product was discovered to be an inhibitor of the serine/threonine phosphatase, calcineurin, and its signaling(More)
Huntington's disease (HD), a genetic neurodegenerative disease caused by a polyglutamine expansion in the Huntingtin (Htt) protein, is accompanied by multiple mitochondrial alterations. Here, we show that mitochondrial fragmentation and cristae alterations characterize cellular models of HD and participate in their increased susceptibility to apoptosis. In(More)
Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins (RCAN1s) have both protective and harmful effects and are implicated in common human pathologies. The mechanisms by which RCAN1s function, however, remain poorly understood. We identify RCAN1s as regulators of mitochondrial autophagy (mitophagy) and demonstrate that induction(More)
The RCAN1 protein (previously called calcipressin 1 or MCIP1) binds to calcineurin, a serine/threonine phosphatase (PP2B), and inhibits its activity. Here we demonstrate that regulated overexpression of an RCAN1 transgene (this gene was previously called DSCR1 or Adapt78) also stimulates expression of the GSK-3beta kinase, which can antagonize the action of(More)
The DSCR1 (Adapt78) gene1 is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac hypertrophy. Calcipressin 1 has been shown to(More)
Oxidized cytoplasmic and nuclear proteins are normally degraded by the proteasome, but accumulate with age and disease. We demonstrate the importance of various forms of the proteasome during transient (reversible) adaptation (hormesis), to oxidative stress in murine embryonic fibroblasts. Adaptation was achieved by 'pre-treatment' with very low(More)
Kelvin J. A. Davies,* Gennady Ermak,* Beverley A. Rothermel, Melanie Pritchard, Joseph Heitman, Joohong Ahnn, Flavio Henrique-Silva, Dana Crawford, Silvia Canaider,** Pierluigi Strippoli,** Paolo Carinci,** Kyung-Tai Min, Deborah S. Fox, Kyle W. Cunningham, Rhonda Bassel-Duby, Eric N. Olson, Zhuohua Zhang, R. Sanders Williams, Hans-Peter Gerber,*** Mercè(More)
We report an entirely new role for the HSP70 chaperone in dissociating 26S proteasome complexes (into free 20S proteasomes and bound 19S regulators), preserving 19S regulators, and reconstituting 26S proteasomes in the first 1-3h after mild oxidative stress. These responses, coupled with direct 20S proteasome activation by poly(ADP ribose) polymerase in the(More)
Although DSCR1 (Adapt78) has been associated with successful adaptation to oxidative stress and calcium stress and with devastating diseases such as Alzheimer's and Down syndrome, no rationale for these apparently contradictory findings has been tested. In fact, DSCR1 (Adapt78) has not yet been proved to provide protection against acute oxidative stress or(More)