Enhanced Ca2+ leak from ER Ca2+ stores induced by hepatitis C NS5A protein.
Enhanced Ca2+ leak from ER Ca2+ stores induced by hepatitis C NS5A protein.
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DOI:
10.1016/j.bbrc.2008.01.127
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发表时间:
2008-04
影响因子:
3.1
通讯作者:
L. C. Robinson;J. Marchant
中科院分区:
文献类型:
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作者:
L. C. Robinson;J. Marchant
The hepatitis C non-structural protein 5A (NS5A) is a Zn2+-binding phosphoprotein essential for viral replication. Expression of NS5A perturbs intracellular Ca2+levels by an undefined mechanism, activating transcription factors implicated in the chronic pathogenesis of hepatitis infections. Here, we demonstrate that regulated expression of NS5A enhanced the passive leak of Ca2+from a subset of the endoplasmic reticulum (ER) Ca2+stores. This action was not replicated by expression of the amphipathic NH2-membrane anchoring domain of NS5A alone, despite targeting to intracellular membranes. Depletion of the NS5A-targeted ER Ca2+store was prevented under conditions of ample ATP supply suggesting compensatory Ca2+ATPase activity, but observed under conditions of ATP insufficiency and in intact cells expressing NS5A.