Project description:The expression of an oncogenic version (G23V mutant) of R-Ras2/TC21 can fully compensate for the loss of the three classical Ras proteins in MEFs. This process involves the inhibition of the antiproliferative p53–p21Cip1 retinoblastoma axis known to cause the morphological and proliferative defects found in Ras-deficient MEFs. Unlike the case of normal MEFs, the inhibition of this antiproliferative pathway by R-Ras2G23V in Ras-deficient cells is mediated by PI3Ka–dependent rather than ERK-dependent signaling inputs. We used microarrays to detail the global programme of gene expression underlying this compensation process.
Project description:The R-RAS2 GTPase has been considered quite similar to classical RAS proteins at the regulatory, signaling, and functional level. The interest in this GTPase has been reinvigorated upon the recent discovery that a long-tail hotspot RRAS2 mutation found in human tumors (Gln72 to Leu) can act as a potent oncogenic driver. Here, we report that the Q72L mutation and other gain-of-function mutations of RRAS2 play roles in tumor initiation and maintenance. Such roles are unlikely to be redundant to those normally executed by classical RAS proteins.
Project description:RAD21 ChIA-PET in human DU 145 cells For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:We performed expression profiling on micro-dissected lung tumors derived from a doxycycline-inducible K-RAS mouse model in order to gain mechanistic insight into K-RAS-mediated tumor maintenance. In this model, the tumors were induced with doxycycline for 11 weeks (in order to obtain lung tumors). At this point the doxycyline was withrawn from the food of the mice and consequently K-RAS inactivated. Thus, the genome-wide analysis was performed on tumors at timepoints 0, 24h and 48h after K-RAS inactivation.
Project description:The goal of this study was to analyse changes of splicing and gene expression induced in IMR90 Control and IMR90 RAS (HRASG12V) cells upon knockdown of splicing factor SF3B1.