Friday, 8 February 2013

Fbxl10 and its role for proper embryonic stem cell differentiation

Researchers from the Biotech Research and Innovation Centre (BRIC) at the University of Copenhagen announced today their findings regarding the Fbxl10 protein, and its importance in the differentiation process of embryonic stem cells (ESCs). The study, may lead to the creation of new cancer treatments.

As we explain in our ESCs article, these stem cells have the capacity to develop into virtually all different types of cells and thus the tissues found in an organism. However, the differentiation process is very complicated, being regulated by many different genes. If something goes wrong, the ESCs lose their ability to differentiate properly, many times leading to the formation of cancer cells.

In this study, the BRIC researchers have found that the Fbxl10 protein is one of the most important regulators for proper differentiation. Kristian Helin, one of the study's chief authors, says that Fbxl10 absence causes embryonic stem cells to differentiate improperly, leading to "developmental defects".

Previous studies have shown that the Polycomb repressive complex 1 (PRC1) is one of the most important genetic switches involved in regulating the pluripotency of embryonic stem cells (ESCs). However, the exact mechanisms controlling its binding to genomic sites and its catalytic activity are poorly understood.

According to Xudong Wu, their findings show that the presence of Fbxl10 is essential for recruiting PRC1 to genes that must be switched off during the differentiation process.

"When PRC1 is bound to DNA it can modify the DNA associated proteins, which lead to silencing of the gene to which it binds" Wu says.

The researchers believe that their study is also very important for cancer research as it indicates that Fbxl10-inhibitors may have anti-cancer potential. They now plan, in collaboration with EpiTherapeutics, to develop Fbxl10-inhibitors as a possible treatment for cancer.

Xudong Wu, Jens Vilstrup Johansen, Kristian Helin. Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation. Molecular Cell, 2013; DOI: 10.1016/j.molcel.2013.01.016

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