Pluto Bioinformatics

GSE121176: Quantitative Analysis of Wild Type CBL, CBL 70Z and Y371S 3T3 Stable Cell Transcriptomes

Bulk RNA sequencing

Cbl (Casitas B-lineage lymphoma) is a prominent post-translational regulator of protein tyrosine kinases (PTKs) that targets activated receptors for ubiquitination-mediated degradation. However, mutations within its E3 ubiquitin ligase activity rendering RING domain are often not sufficient to induce transformation. Rather, a conserved residue (Y371) within the linker helix region (LHR) of Cbl has been a mutational hotspot in myeloproliferative diseases. Interestingly, phosphorylation of Y371 is a prerequisite for Cbls ability to ubiquitinate PTKs. We have previously shown that Y371 mutations affect the conformation of Cbl that can be related to its transformation potential. We wanted to investigate for any additional advantage that the Cbl-Y371 mutants could gain over their wild-type counterpart so as to explain their oncogenicity. In our current study, we wanted to investigate the transcriptome profiles of cells overexpressing WT CBL or CBL-70Z, a well-characterized oncogenic CBL mutant lacking residues 366-382 and Y371S a prevalent MDS/MPN CBL mutant. We found an interesting inverse correlationship between the transcriptome of cells expressing WT CBL and the mutant CBLs. The results from this study can be linked to the oncogenic abilities of the mutant CBLs. SOURCE: Syed,Feroj,Ahmed (f.syed@beatson.gla.ac.uk) - Ubiquitin Signaling (Danny Huang) Beatson Institute for Cancer Research