• Home
  • About
  • Members
  • Publications
  • Funding
  • News and Pictures
  • Contact
Dykhuizen Lab

News and Pictures

Libby and Alisha's Polybromo-1 paper is published!

5/31/2019

0 Comments

 
PBRM1 will be the death of me. It is a beautiful but poorly behaved protein. We've spent years trying to pin down reliable phenotypes in renal cancer that relate to specific biochemical function and have been humbled again and again. We've found dozens of cell lines with no detectable PBRM1 knockout phenotype. Then we've defined a phenotype in one cell line only to find a completely different phenotype in a very similar cell line.  Then  to make things worse, we've identified a phenotype in a cell line, only to find that phenotype lost or completely reversed when we take the knockout cell line back out of storage. 

While we all know by now that chromatin regulators have context-dependent function, we really need to pin down this context in order to figure out how PBRM1 acts as a tumor suppressor in renal cancer (and other cancers). So in this paper we went back to untransformed cells to define PBRM1's role in maintaining epithelial cell maintenance. To make a long story short (if you want the long version, it is all in the paper) we find that PBRM1 maintains the expression of stress response genes in epithelial cells. Under low stress conditions loss of PBRM1 is growth-promoting, but under high stress conditions  PBRM1 is cytoprotective and is required for the induction of stress response genes, the reduction of reactive oxygen species, and, eventually the initiation of apoptotic pathways.  Now that we've found this, we understand why the same cell line responds differently to PBRM1 loss depending on the cell culture conditions, and why cell lines with inherently high internal stress (oxidative stress or oncogene addition) are so sensitive to PBRM1 knockdown.

It's been a frustrating process, but a fruitful one (I think). Now we can start to piece together how PBRM1 responds to environmental signals to change gene expression. We have a lot of work to do, but I am hopeful that we have model that can explain all the varied and contradictory phenotypes reported for PBRM1. 

"PBRM1 Regulates Stress Response in Epithelial Cells."
​https://www.ncbi.nlm.nih.gov/pubmed/31077944
Picture
0 Comments



Leave a Reply.

    Author

    Dykhuizen Lab News

    Archives

    July 2022
    April 2022
    May 2021
    February 2021
    May 2019
    April 2019
    March 2019
    February 2019
    January 2019
    December 2018
    November 2018
    June 2018
    April 2018
    February 2018
    January 2018
    October 2017
    September 2017
    August 2017
    May 2017
    January 2017
    December 2016
    November 2016
    October 2016
    September 2016
    August 2016
    June 2016
    May 2016
    April 2016
    January 2016
    December 2015
    August 2015
    April 2015
    March 2015
    January 2015
    November 2014
    September 2014
    June 2014
    May 2014
    January 2014
    December 2013
    November 2013
    August 2013

    Categories

    All

    RSS Feed

Powered by Create your own unique website with customizable templates.
  • Home
  • About
  • Members
  • Publications
  • Funding
  • News and Pictures
  • Contact