Abstract
The invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of malignant process, yet the molecular mechanisms that dictate this locally invasive behavior remain poorly understood. Over-expression of PIAS3 effectively changes cell shape and inhibits GBM cell migration. We focused on the molecular target(s) of PIAS3 stimulated sumoylation, which play an important role in the inhibition of GBM cell motility. Here we report, through the immunoprecipitation with SUMO1 antibody, followed by proteomic analysis, the identification of vimentin (vimentin354), a nuclear component in GBM cells, as the main target of sumoylation promoted by PIAS3.
Highlights
Glioblastoma multiforme (GBM) represents 29% of all primary brain tumors or 5,000 new cases per year in the United States [1]
Recent work has revealed that Protein Inhibitor of Activated STAT3 (PIAS3) acts as an E3-like ligase to stimulate the attachment of small ubiquitin-like modifier (SUMO) to target proteins, which act in such important cellular pathways as Wnt signaling, the p53 pathway and steroid hormone signaling [9, 10]
To characterize glioblastoma multiforme (GBM)’s extreme migration potential, we focused on the effect of PIAS3stimulated sumoylation on the inhibition of GBM cell migration
Summary
Glioblastoma multiforme (GBM) represents 29% of all primary brain tumors or 5,000 new cases per year in the United States [1]. The infiltrative growth pattern of these tumors precludes curative neurosurgery and no therapeutic modality has substantially changed the outcome of patients with GBM [2]. A main characteristic of GBM is the cells’ extreme migration potential and topographical diffuse nature, resulting in the inability to completely dissect GBM tumors [6]. New effective therapeutic modalities for advanced and invasive GBM are desperately needed. Protein Inhibitor of Activated STAT3 (PIAS3) was first identified as a specific inhibitor by blocking the DNA-binding activity of STAT3 and inhibiting STAT3mediated gene activation [7]. PIAS3 acts as a binding protein of other transcriptional regulators such as androgen receptor, TIF2, and NF-kappaB [9]. Recent work has revealed that PIAS3 acts as an E3-like ligase to stimulate the attachment of small ubiquitin-like modifier (SUMO) to target proteins, which act in such important cellular pathways as Wnt signaling, the p53 pathway and steroid hormone signaling [9, 10]
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