Phos enzyme ID'd using CRISPR may lead to safer cancer meds say researchers

Phosphorylation - the addition of a phosphate group to a molecule - controls the activity of proteins produced inside cells. The extra phosphate group can - for example - activate or turn off an enzyme or guide a protein's migration.

Secreted proteins are also phosphorylated, however, until now little was known about the enzymes involved in the process.

This week​ researchers from the University of California, San Diego School of Medicine announced that a single enzyme - Fam20C - is responsible for the phosphorylation of more than 100 secreted proteins in a paper in the Journal Cell.

Gene editing ​

The team used CRISPR/Cas9 gene editing to delete the Fam20C gene from liver, breast and bone cancer cells and observed that proteins secreted by the modified cells were not phosphorylated. 

They finding could result in new oncology drugs because Fam20C is overexpressed by cancerous cells explained co-lead author Vincent Tagliabracci.

“At first glance, it appears that Fam20C would not be a great target due to the wide variety of substrates that it phosphorylates. One would expect multiple off-target effects and would likely have a detrimental effect on biomineralization as seen in patients with Raine syndrome.​ 

“However," ​Tagliabracci continued "specifically targeting a Fam20C inhibitor to tumors would likely reduce the off-target effects and may be beneficial in slowing cancer cell metastasis​."

Targeting the enzyme could also provide a new treatment option for patients with osteoporosis according to Tagliabracci who said: “A Fam20C activator targeted to bone would—theoretically—increase bone density and perhaps be efficacious for patients​.”

Tagliabracci told BioPharma-reporter.com the research has already attracted interest from the pharmaceutical industry.

Source: Cell​

A Single Kinase Generates the Majority of the Secreted Phosphoproteome​

DOI: http://dx.doi.org/10.1016/j.cell.2015.05.028​