(A) Gene ontology (GO) distribution of the global proteome of HEK293 cells expressing cyclin F variants under the “Protein Class” category demonstrating proteins are classified as having molecular functions: nucleic acid binding, hydrolase, and transferase activity. (B) Selected gene ontology (GO) annotations of unique proteins clustered to selected pathways in neuroinflammation and ALS signalling. (C) Ingenuity pathway analysis (IPA) of the proteomic profile of cyclin F variants predicts activation and inhibition of various canonical cellular pathways. Apoptosis signaling was predicted to be activated in cells expressing cyclin F K97R, S195R, and S621G. Orange and blue annotation refer, respectively, to predicted activation and inhibition as determined by IPA. (D) Heatmap of label-free proteomics of differentially expressed proteins in the apoptosis signaling pathway and IPA prediction of downstream effects (log2 values shown; values shown as 5 and −5, respectively, indicate detection of the presence and absence of a protein and are not measured values). Red and green annotations refer, respectively, to experimentally measured values. Orange and blue annotations and lines refer, respectively, to predicted activation and inhibition as determined by IPA. Filled and dashed lines, respectively, refer to direct and indirect causal relationships.
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