Low density @entity8993 ( @entity8993 ) is a transmembrane receptor, localized mainly in hepatocytes, fibroblasts, and neurons. It is implicated in diverse biological processes both as an endocytic receptor and as a signaling molecule. Recent reports show that @entity8993 undergoes sequential proteolytic cleavage in the ectodomain and transmembrane domain. The latter cleavage, mediated by the Alzheimer-related gamma-secretase activity that also cleaves amyloid precursor protein (APP) and Notch, results in the release of the @entity8993 cytoplasmic domain (LRPICD) fragment. This relatively small cytoplasmic fragment has several motifs by which @entity8993 interacts with various intracellular adaptor and scaffold proteins. However, the function of this fragment is largely unknown. Here we show that the LRPICD is translocated to the nucleus, where it colocalizes in the nucleus with a transcription modulator, @entity24377 , which is known to interact with @entity56549 and with the APP-derived intracellular domain. LRPICD dramatically inhibits APP-derived intracellular domain/ @entity56549 transactivation mediated by @entity24377 . LRPICD has a close interaction with @entity24377 in the nucleus, as shown by a fluorescence resonance energy transfer assay. These observations suggest that LRPICD has a novel signaling function, negatively impacting transcriptional activity of the APP, @entity56549 , and @entity24377 complex in the nucleus, and shed new light on the function of @entity8993 in transcriptional modulation.

The intracellular domain of the low density lipoprotein receptor-related protein modulates transactivation mediated by amyloid precursor protein and XXXX .

@entity8993 :: ('4035', 'Gene') :: ['lipoprotein-related protein', 'LRP'] @entity24377 :: ('10524', 'Gene') :: ['Tip60'] @entity56549 :: ('322', 'Gene') :: ['Fe65']
@entity56549 :: (322,Gene) :: ['Fe65']
