Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1. | Blasius et al. Genome Biology 2011 12 R78 http content 12 8 R78 Genome Biology RESEARCH Open Access A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1 11 11 1 2 2 Melanie Blasius Josep V Forment Neha Thakkar Sebastian A Wagner Chunaram Choudhary and Stephen P Jackson1 Abstract Background The cell-cycle checkpoint kinase Chk1 is essential in mammalian cells due to its roles in controlling processes such as DNA replication mitosis and DNA-damage responses. Despite its paramount importance how Chk1 controls these functions remains unclear mainly because very few Chk1 substrates have hitherto been identified. Results Here we combine a chemical genetics approach with high-resolution mass spectrometry to identify novel Chk1 substrates and their phosphorylation sites. The list of targets produced reveals the potential impact of Chk1 function not only on processes where Chk1 was already known to be involved but also on other key cellular events such as transcription RNA splicing and cell fate determination. In addition we validate and explore the phosphorylation of transcriptional co-repressor KAP1 Ser473 as a novel DNA-damage-induced Chk1 site. Conclusions By providing a substantial set of potential Chk1 substrates we present opportunities for studying unanticipated functions for Chk1 in controlling a wide range of cellular processes. We also refine the Chk1 consensus sequence facilitating the future prediction of Chk1 target sites. In addition our identification of KAP1 Ser473 phosphorylation as a robust readout for Chk1 activity could be used to explore the in vivo effects of Chk1 inhibitors that are being developed for clinical evaluation. Background Protein phosphorylation is an abundant post-translational modification that plays crucial roles in essentially all cellular processes including the DNA-damage response DDR . Key aspects of the DDR are the slowing or stopping of cell cycle progression by DNA-damage checkpoint .
