EMBO J 2006,
PMID: 16902409
He, Cheng; Schneider, Robert
Short-lived cytokine mRNAs contain an AU-rich destabilizing element (ARE). AUF1 proteins bind the ARE, undergo shuttling, and promote cytoplasmic ARE-mRNA decay through a poorly understood mechanism. We therefore identified AUF1-interacting proteins that may play a role in ARE-mRNA decay. We used mass-spectrometry to identify 14-3-3sigma protein as an AUF1-interacting protein. 14-3-3sigma binds selectively and strongly to p37 AUF1 and to a lesser extent to the p40 isoform, the two isoforms most strongly associated with ARE-mRNA decay, but not to the two larger isoforms, p42 and p45. The 14-3-3sigma interaction site on p37 was mapped to a region found only in the two smaller AUF1 isoforms and which overlaps a putative nuclear localization signal (NLS). Stable overexpression of 14-3-3sigma significantly increased cytoplasmic accumulation of p37 AUF1 and reduced the steady-state level and half-life of a reporter ARE-mRNA. siRNA silencing of AUF1 eliminated the effect of 14-3-3sigma overexpression. 14-3-3sigma therefore binds to p37 AUF1, retains it in the cytoplasm probably by masking its NLS, and enhances rapid turnover of ARE-mRNAs.
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Text Mining Data
ARE-mRNA decay → AUF1: "
AUF1 proteins bind the ARE, undergo shuttling, and
promote cytoplasmic
ARE-mRNA decay through a poorly understood mechanism
"
Manually curated Databases
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IRef Biogrid Interaction:
SFN
—
HNRNPD
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
SFN
—
HNRNPD
(direct interaction, pull down)
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IRef Biogrid Interaction:
HNRNPD
—
PABPC1
(physical association, affinity chromatography technology)
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IRef Intact Interaction:
HNRNPD
—
YWHAG
(direct interaction, pull down)
-
IRef Intact Interaction:
YWHAZ
—
HNRNPD
(direct interaction, pull down)
-
IRef Intact Interaction:
HNRNPD
—
YWHAH
(direct interaction, pull down)
-
IRef Intact Interaction:
HNRNPD
—
SFN
(direct interaction, pull down)
-
IRef Intact Interaction:
HNRNPD
—
SFN
(physical association, pull down)
-
IRef Intact Interaction:
HNRNPD
—
SFN
(physical association, anti bait coimmunoprecipitation)
-
IRef Intact Interaction:
SFN
—
HNRNPD
(direct interaction, pull down)
In total, 5 gene pairs are associated to this article in curated databases