A novel function of 14-3-3 protein: 14-3-3zeta is a heat-shock-related molecular chaperone that dissolves thermal-aggregated proteins.
The 14-3-3 proteins are highly conserved molecules that function as intracellular adaptors in a variety of biological processes, such as signal transduction, cell cycle control, and apoptosis. Here, we show that a 14-3-3 protein is a heat-shock protein (Hsp) that protects cells against physiological stress as its new cellular function. We have observed that, in Drosophila cells, the 14-3-3zeta is up-regulated under heat stress conditions, a process mediated by a heat shock transcription factor. As the biological action linked to heat stress, 14-3-3zeta interacted with apocytochrome c, a mitochondrial precursor protein of cytochrome c, in heat-treated cells, and the suppression of 14-3-3zeta expression by RNA interference resulted in the formation of significant amounts of aggregated apocytochrome c in the cytosol. The aggregated apocytochrome c was converted to a soluble form by the addition of 14-3-3zeta protein and ATP in vitro. 14-3-3zeta also resolubilized heat-aggregated citrate synthase and facilitated its reactivation in cooperation with Hsp70/Hsp40 in vitro. Our observations provide the first direct evidence that a 14-3-3 protein functions as a stress-induced molecular chaperone that dissolves and renaturalizes thermal-aggregated proteins.
Yano
Mihiro
M
Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
Nakamuta
Shinichi
S
Wu
Xueji
X
Okumura
Yuushi
Y
Kido
Hiroshi
H
D048948:14-3-3 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D006979:Hyperthermia, Induced; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D013696:Temperature; D014158:Transcription, Genetic
D048948:14-3-3 Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011498:Protein Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D045304:Cytochromes c; D002950:Citrate (si)-Synthase