Expanding the substantial interactome of NEMO using protein microarrays.

PloS One
Beau J FennerJochen H M Prehn

Abstract

Signal transduction by the NF-kappaB pathway is a key regulator of a host of cellular responses to extracellular and intracellular messages. The NEMO adaptor protein lies at the top of this pathway and serves as a molecular conduit, connecting signals transmitted from upstream sensors to the downstream NF-kappaB transcription factor and subsequent gene activation. The position of NEMO within this pathway makes it an attractive target from which to search for new proteins that link NF-kappaB signaling to additional pathways and upstream effectors. In this work, we have used protein microarrays to identify novel NEMO interactors. A total of 112 protein interactors were identified, with the most statistically significant hit being the canonical NEMO interactor IKKbeta, with IKKalpha also being identified. Of the novel interactors, more than 30% were kinases, while at least 25% were involved in signal transduction. Binding of NEMO to several interactors, including CALB1, CDK2, SAG, SENP2 and SYT1, was confirmed using GST pulldown assays and coimmunoprecipitation, validating the initial screening approach. Overexpression of CALB1, CDK2 and SAG was found to stimulate transcriptional activation by NF-kappaB, while SYT1 overexpression ...Continue Reading

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Citations

Jul 5, 2013·Science Translational Medicine·Elinor K KarlssonRegina C Larocque
Apr 12, 2013·Expert Review of Proteomics·Ellen Niederberger, Gerd Geisslinger
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Oct 26, 2012·Journal of Cell Science·Hans-Georg KönigJochen H M Prehn
Jul 16, 2021·Frontiers in Molecular Neuroscience·Rithvik R NalamalapuMargaret S Saha

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Methods Mentioned

BETA
Protein Arrays
ubiquitination
pulldown
coimmunoprecipitation
two-hybrid
protein array
immunoprecipitation
transfection
gene knockdown
size exclusion filtration

Software Mentioned

NEMO
Invitrogen Protoarray Prospector
ProtoArray
Invitrogen Prospector

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