Protein Posttranslational Modifications in Glioma Stem Cells

Glioblastoma (GBM) is the most malignant form of glioma. Glioma stem cells (GSCs) contribute to the initiation, progression, and recurrence of GBM via their self-renewal potential and tumorigenicity. This review presents a brief overview of the influences of two protein posttranslational modifications in GSCs on the properties of GSCs and malignancy of GBM: (I) the ubiquitination of transforming growth factor (TGF)-β receptor (TGFBR) by SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) and (II) the phosphorylation of extracellular signal-regulated kinase 5 (ERK5) by mitogen-activated protein kinase/ERK kinase 5 (MEK5). The phosphorylation state of SMURF2Thr249 regulates the stemness and tumorigenicity of GSCs via the ubiquitin-dependent modification of the TGFBR-SMAD-SOX axis, along with the downregulation of SMURF2Thr249 phosphorylation in patients with GBM. MEK5 controls the self-renewal and tumorigenic potential of GSCs by phosphorylating the ERK5-signal transducer and activator of transcription 3 (STAT3) axis concomitant with high expression and activity of ERK5 in GSCs. These findings contributed to our understanding of the molecular mechanisms underlying the maintenance of the stemness and tumorigenicity of GSCs through protein posttranslational modifications. We propose that these two protein posttranslational modifications in GSCs might be explored as an effective therapeutic approach against various cancers whose malignancies are associated with the stemness of cancer stem cells.