The p90 ribosomal S6 kinase–UBR5 pathway controls Toll-like receptor signaling via miRNA-induced translational inhibition of tumor necrosis factor receptor–associated factor 3

Abstract

MicroRNAs (miRNAs) are small, noncodingRNAs that post-transcriptionally regulate gene expression. For example, miRNAs repress gene expression by recruiting the miRNA-induced silencing complex (miRISC), a ribonucleoprotein complex that contains miRNA-engaged Argonaute (Ago) and the scaffold protein GW182. Recently, ubiquitin protein ligase E3 component N-recognin 5 (UBR5) has been identified as a component of miRISC. UBR5 directly interacts with GW182 proteins and participates in miRNA silencing by recruiting downstream effectors, such as the translation regulator DEAD-box helicase 6 (DDX6) and transducer of ERBB2.1/2 (Tob1/2), to the Ago-GW182 complex. However, the regulation of miRISC-associated UBR5 remain largely elusive. In the present study, we show that UBR5 downregulates the levels of TNF receptor-associated factor 3 (TRAF3), a key component of toll-like http://www.jbc.org/cgi

UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy

“…for gene TRAF3) (Cho et al . ). However, UBR5 has also been shown to ubiquitinylate Groucho/TLE, comprising repressors of transcription, and thus subsequently activate transcription of Armadillo/β‐catenin (Flack et al .…”

“…Other studies also suggest that the protein activity of UBR5 was important, as a result of phosphorylation by p90RSK (Cho et al . ) and mitogen‐activated protein kinase 1 [extracellular signal regulated kinase (ERK)2] in cells in response to epidermal growth factor (Eblen et al . ).…”

“…Interestingly, previous studies have suggested that UBR5 translocates into the nucleus in a complex that can silence transcription (e.g. for gene TRAF3) (Cho et al 2017). However, UBR5 has also been shown to ubiquitinylate Groucho/TLE, comprising repressors of transcription, and thus subsequently activate transcription of Armadillo/β-catenin (Flack et al 2017).…”

“…Therefore, these interactions warrant further investigation in models of skeletal muscle anabolism and hypertrophy. Other studies also suggest that the protein activity of UBR5 was important, as a result of phosphorylation by p90RSK (Cho et al 2017) and mitogen-activated protein kinase 1 [extracellular signal regulated kinase (ERK)2] in cells in response to epidermal growth factor (Eblen et al 2003). Where ERK is a well-established regulator of muscle cell proliferation (Foulstone et al 2004) and load-induced hypertrophy , and p90RSK is important for protein synthesis in skeletal muscle tissue (Moore et al 2011).…”

UBR5 is a Novel E3 Ubiquitin Ligase involved in Skeletal Muscle Hypertrophy and Recovery from Atrophy

“…Indeed, a similar observation of no increase in gene expression but increases at the protein level occurred during human muscle cell differentiation. Previous studies have suggested UBR5 translocates into the nucleus in a complex that can silence transcription, for example the gene TRAF3 (Cho et al, 2017). However, has also been shown to ubiquitinylate Groucho/TLE's that are repressors of transcription and thus subsequently activate transcription of Armadillo/β-catenin (Flack et al, 2017).…”