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The Cytoplasmic Engulfment Protein Elmo1 Interacts With the Mediator Complex Subnit Med31

Mauldin, Joshua Post
Format
Thesis/Dissertation; Online
Author
Mauldin, Joshua Post
Advisor
Ravichandran, Kodi
Abstract
The cytoplasmic Elmo1:Dock180 complex acts as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac and functions downstream of the phagocytic receptor BAI1 during apoptotic cell clearance, and in the entry of Salmonella and Shigella into cells [1-7]. We discovered an unexpected binding between Elmo1 and Mediator complex subunit Med31. The Mediator complex is a regulatory hub for nearly all gene transcription via RNA polymerase II (Pol II), bridging the general transcription machinery with gene-specific regulatory proteins [8-14]. Med31 is the smallest and the most evolutionarily conserved Mediator subunit [15, 16] and knockout of Med31 results in embryonic lethality in mice [17]; however, Med31 function in specific biological contexts is not understood. We observed that in primary macrophages, during Salmonella infection, Elmo1 and Med31 specifically affected expression of cytokine genes Il10 and Il33 among the >25 genes monitored. While endogenous Med31 is predominantly nuclear localized, Elmo1 increased the cytoplasmic localization of Med31. We discover ubiquitination as a novel post-translational modification of Med31, with the cytoplasmic mono-ubiquitinated form of Med31being enhanced by Elmo1. These data identify Elmo1 as a novel regulator of Med31, revealing a previously unrecognized link between cytoplasmic signaling proteins and the Mediator complex. Note: Abstract extracted from PDF text
Language
English
Published
University of Virginia, Department of Cell Biology, PHD, 2012
Published Date
2012-12-01
Degree
PHD
Collection
Libra ETD Repository
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