The LIM domain protein nTRIP6 modulates the dynamics of myogenic differentiation.

The process of myogenesis which operates during skeletal muscle regeneration involves the activation of muscle stem cells, the so-called satellite cells. These then give rise to proliferating progenitors, the myoblasts which subsequently exit the cell cycle and differentiate into committed precursors, the myocytes. Ultimately, the fusion of myocytes leads to myofiber formation.

The LIM domain protein nTRIP6 acts as a co-repressor for the transcription factor MEF2C in myoblasts.

The transcription factor Myocyte enhancer factor 2C (MEF2C) plays a key role in the late differentiation of skeletal muscle progenitor cells, the so-called myoblasts. During myoblast differentiation, both MEF2C expression and transcriptional activity are regulated. We have reported that nTRIP6, the nuclear isoform of the focal adhesion LIM domain protein TRIP6, acts as an adaptor transcriptional co-activator for several transcription factors.

The LIM domain protein nTRIP6 recruits the mediator complex to AP-1-regulated promoters.

Several LIM domain proteins regulate transcription. They are thought to act through their LIM protein-protein interaction domains as adaptors for the recruitment of transcriptional co-regulators. An intriguing example is nTRIP6, the nuclear isoform of the focal adhesion protein TRIP6.

The nuclear isoform of the LIM domain protein Trip6 integrates activating and repressing signals at the promoter-bound glucocorticoid receptor.

Trip6 belongs to a family of cytosolic LIM domain proteins involved in cell adhesion and migration. Recent findings show that these proteins also regulate transcription. We have previously reported that nTrip6, a nuclear isoform of Trip6, acts as a co-activator for AP-1 and NF-kappaB transcription factors.

Restriction to Fos family members of Trip6-dependent coactivation and glucocorticoid receptor-dependent trans-repression of activator protein-1.

The term activator protein (AP)-1 describes homodimeric and heterodimeric transcription factors composed of members of the Jun, Fos, and cAMP response element-binding protein (CREB)/activating transcription factor (ATF) families of proteins. Distinct AP-1 dimers, for instance the prototypical c-Jun:c-Fos and c-Jun:ATF2 dimers, are differentially regulated by signaling pathways and bind related yet distinct response elements in the regulatory regions of AP-1 target genes. Little is known about the dimer-specific regulation of AP-1 activity at the promoter of its target genes.

A nuclear isoform of the focal adhesion LIM-domain protein Trip6 integrates activating and repressing signals at AP-1- and NF-kappaB-regulated promoters.

Glucocorticoid receptor (GR)-mediated transrepression of the transcription factors AP-1 and NF-kappaB, responsible for most of the anti-inflammatory effects of glucocorticoids, is initiated by the tethering of GR to the promoters of target genes. We report that this tethering is mediated by a nuclear isoform of the focal adhesion LIM domain protein Trip6. Trip6 functions as a coactivator for both AP-1 and NF-kappaB.