In PNAS this week, scientists led by those at the University of Toronto have used proteomic profiling to find links between phosphotyrosine and FGFR3 expression in multiple myeloma. Using mass spec, they identified phosphotyrosine sites regulated by FGFR3 activation and inhibition in KMS11 myeloma cells. FGF receptor-3 is a drug target in a subset of human multiple myelomas and is activated in some cervical and colon and many bladder cancers and in some skeletal dysplasias, they say in the abstract.
In a paper from scientists at Weill Medical College of Cornell University, scientists present and describe "N-CLAP (N-terminalomics by chemical labeling of the α-amine of proteins), a general approach for profiling protein N-termini and identifying protein cleavage sites during cellular signaling." The method allowed them to profile 278 peptides, finding cleavage events linked to methionine aminopeptidases and signal peptide peptidases, and proteins that are cleaved after cisplatin-induced apoptosis.
David Cortez at Vanderbilt University School of Medicine is lead author on work that used functional genomic screens, including both RNAi and cDNA screens, to find proteins at work in the DNA damage response. The RNAi screen identified 73 genes that cause DDR activation when silenced, including the cell-cycle checkpoint protein CDK2-interacting protein (CINP).
Scientists led by those at the Spanish National Cancer Centre in Madrid have found that telomere shortening causes global changes in transcription. Using a transgenic mouse mode deficient in telomerase, they found that telomere shortening is accompanied by a "gradual deregulation of the mammalian transcriptome leading to cumulative changes in a defined set of genes, including up-regulation of the mTOR and Akt survival pathways and down-regulation of cell cycle and DNA repair pathways," they say, which ultimately aids in the aging process.