Monday, August 5, 2013

HOW FAST MEMBRANE EVENTS REACH THE NUCLEUS, LIKE LIGHTNING FAST!

"Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso.

Source

Department of Biology, LSB-331, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4K1. danielj@mcmaster.ca

Abstract

The catenin p120 (hereafter p120(ctn)) was first identified as a Src kinase substrate and subsequently characterized as an Armadillo catenin member of the cell-cell adhesion cadherin-catenin complex. In the past decade, many studies have revealed roles for p120(ctn) in regulating Rho family GTPase activity and E-cadherin stability and turnover, events that occur predominantly at the plasma membrane or in the cytoplasm. However, the recent discovery of the nuclear BTB/POZ-ZF transcription factor Kaiso as a p120(ctn) binding partner, coupled with the detection of p120(ctn) in the nucleus of some cell lines and tumor tissues, suggested that like the classical beta-catenin, p120(ctn) undergoes nucleocytoplasmic trafficking and regulates gene expression. Indeed, p120(ctn) has a classic nuclear localization signal and does traffic to the nucleus. Moreover, nuclear p120(ctn) regulates Kaiso DNA-binding and transcriptional activity, similar to beta-catenin's modulation of TCF/LEF transcription activity. However unlike beta-catenin, p120(ctn) does not appear to be a transcriptional activator. Hence it remains to be determined whether the sole role of nuclear p120(ctn) is regulation of Kaiso or whether p120(ctn) binds and regulates other transcription factors or nuclear proteins."
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This article, easily found on Google, is an important example of how fast events  happening at the membrane reach the the depth of the cell at nuclear level.  Indeed E-cadherin is an adhesion protein which is found at the cellular surface, intervening in the the cell to cell interaction.  YET, its interaction with the Kaiso "as a binding partner", put it center to epigenetic events in the cell making the Kaiso a target to stop nuclear effects of E-Cadherins.
Regulation of the Rho is indeed another very significant point, since the Rho is now well known to heavily contribute to proliferation and metastatic potential of malignant cells.
The Kaiso is known to : (Wipedia)

"ZBTB33 has been shown to interact with HDAC3,[2] Nuclear receptor co-repressor 1[2] and CTNND1.[3]"
again re-enforcing the notion that membrane events can join the epigenetic ones in a FLASH! 

We thank these researchers for advancing medicine ! 

(careful now if you hit the Ku Antigen, you will affect, the PARP1, G quadruplex, and c-MYC, the amplifier ! and therefore KRAS at the membrane, again!)

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