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A RING to rule them all? Insights into the Map3k1 PHD motif provide a new
mechanistic understanding into the diverse roles of Map3k1
#MMPMID25613373
Suddason T
; Gallagher E
Cell Death Differ
2015[Apr]; 22
(4
): 540-8
PMID25613373
show ga
Despite the sizable number of components that comprise Mapk cascades, Map3k1 is
the only element that contains both a kinase domain and a plant homeodomain (PHD)
motif, allowing Map3k1 to regulate the protein phosphorylation and ubiquitin
proteasome systems. As such, Map3k1 has complex roles in the regulation of cell
death, survival, migration and differentiation. Numerous mouse and human genetic
analyses have demonstrated that Map3k1 is of critical importance for the immune
system, cardiac tissue, testis, wound healing, tumorigenesis and cancer. Recent
gene knockin of Map3k1 to mutate the E2 binding site within the Map3k1 PHD motif
and high throughput ubiquitin protein array screening for Map3k1 PHD motif
substrates provide critical novel insights into Map3k1 PHD motif signal
transduction and bring a brand-new understanding to Map3k1 signaling in mammalian
biology.