Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53

• DOI: 10.1038/cddis.2015.117
• Publication Date: 2015-05-21T12:54:17Z
• Authors: A Desantis; T Bruno; V Catena; F De Nicola; F Goeman; S Iezzi; C Sorino; M P Gentileschi; S Germoni; V Monteleone; M Pellegrino; M Kann; P D De Meo; M Pallocca; K Höpker; F Moretti; E Mattei; H C Reinhardt; A Floridi; C Passananti; T Benzing; G Blandino; M Fanciulli
• Keywords: p53; 0301 basic medicine; DNA Repair; Apoptosis; Mice, Transgenic; DDR; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; RNA, Small Interfering; Thymocytes; BRCA1 Protein; apoptosis; Cell Cycle Checkpoints; HCT116 Cells; Enzyme Activation; Repressor Proteins; Gene Expression Regulation; Che-1; MCF-7 Cells; Original Article; RNA Interference; Apoptosis Regulatory Proteins; DNA Damage; Protein Binding

Abstract The tumor suppressor p53 is mainly involved in the transcriptional regulation of a large number growth-arrest- and apoptosis-related genes. However, clear understanding which factor/s influences choice between these two opposing p53-dependent outcomes remains largely elusive. We have previously described that response to DNA damage, RNA polymerase II-binding protein Che-1/AATF transcriptionally activates p53. Here, we show Che-1 binds directly This interaction essentially occurs first hours whereas it lost when cells undergo apoptosis posttranscriptional modifications. Moreover, sits ternary complex with oncosuppressor Brca1. Accordingly, our analysis genome-wide chromatin occupancy by revealed p53/Che1 results preferential transactivation growth arrest target genes over its pro-apoptotic Notably, exposure +/− mice ionizing radiations resulted enhanced thymocytes, compared WT mice. These confirm as an important regulator activity suggest be promising yet attractive drug for cancer therapy.