Peer-Reviewed Journal Details
Mandatory Fields
Neasta J, Kiely PA, He DY, Adams DR, O'Connor R, Ron D
The Journal of Biological Chemistry
Direct interaction between the scaffolding proteins RACK1 and 14-3-3ζ regulates brain-derived neurotrophic factor (BDNF) transcription.
Optional Fields
RACK1 is a scaffolding protein that spatially and temporally regulates numerous signaling cascades. We previously found that activation of the cAMP signaling pathway induces the translocation of RACK1 to the nucleus. We further showed that nuclear RACK1 is required to promote the transcription of the brain-derived neurotrophic factor (BDNF). Here, we set out to elucidate the mechanism underlying cAMP-dependent RACK1 nuclear translocation and BDNF transcription. We identified the scaffolding protein 14-3-3ζ, as a direct binding partner of RACK1. Moreover, we found that 14-3-3ζ is necessary for the cAMP-dependent translocation of RACK1 to the nucleus. We further observed that the disruption of RACK1/14-3-3ζ interaction with a peptide derived from the RACK-1/14-3-3ζ binding site, or shRNA-mediated 14-3-3ζ knock-down inhibits cAMP induction of BDNF transcription. Together, these data reveal that the function of nuclear RACK1 is mediated through its interaction with 14-3-3ζ. Furthermore, the interaction between two multifunctional scaffolding proteins, RACK1 and 14-3-3ζ, can provide a multiprotein signaling platform to tether signalosome.
doi: 10.1074/jbc.M111.272195
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