Paper from Department of Pharmacy published in Molecular Cell – University of Copenhagen

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14 December 2017

Paper from Department of Pharmacy published in Molecular Cell

Article

An article by i.a. PhD student Ingvar Möller and Professor MSO Kasper Rand, Department of Pharmacy, has been published in Molecular Cell, a top journal of molecular biology.

Professor MSO Kasper Dyrberg RandAn article by i.a. PhD student Ingvar Rúnar Möller and Professor MSO Kasper Dyrberg Rand, Department of Pharmacy, has been published in Molecular Cell, a top journal of molecular biology (IF  14).

The work is a research collaboration with Professor Andreas Ladurner at Ludwig-Maximilians University Munchen with whom Kasper Rand share corresponding authorship on the paper. 

In short, the work provides a new molecular understanding of the function of a protein (ALC1) involved in chromatin remodeling and cancer – for instance, using HDX-MS, we identify three regions involved in the transition from an inactive to active state of the protein.
This could open up for the first therapeutic strategies to target this protein:
"Our analysis identifies how the oncogene ALC1 might be targeted in cancer. Small molecules that inhibit its allostery or activity should reproduce ALC1 knockdown phenotypes, such as reduced tumor growth, reduced reprogramming, and increased sensitivity to chemotherapy (Jiang et al., 2015; Liu et al., 2016). Compounds that stabilize the inactive, gated conformation of ALC1, which lower its catalytic activity or that disrupt its ability to recognize PAR should suppress the potent chromatin relaxation activity of this oncogene".

Molecular Cell; vol. 68/5, 7 December 2017. Pages 860–871.e7:
A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene.