"We compared a number of different things," adds Clohessy. "We compared different cancer cell lines. We looked at changes to the riboproteome within a single specific cell line, both with and without use of a pharmacological inhibitor. And, we looked at a cell line in the context of genetic alteration. We essentially got a clear snapshot of which proteins were in this space at any particular time, and saw how they responded to cellular signals and stresses."
The authors then carried out a computational analysis on this extensive dataset to determine if there were specific protein networks or pathways that were highly represented in the data. Their survey revealed a number of exciting and surprising findings with important therapeutic implications.
"Among other things, our analysis uncovered a high incidence of genetic alterations to the riboproteome components in cancer, with a distinct bias towards genetic amplification, [whereby cells accumulate multiple copies of genes which can support cancer growth and survival]" explains Reschke, adding that it also revealed the presence of a significant population of RNA binding proteins (RBPs), important regulators of mRNA translation, some of which are also associated with disease.
"Changes in ribosome amounts have been shown to be associated with cancer for more than a century," notes Nahum Sonenberg, PhD, James McGill Professor of Biochemistry at McGill University. "However, the mechanism that links ribosomes and cancer is not well understood. This paper f
|Contact: Bonnie Prescott|
Beth Israel Deaconess Medical Center