The role of Calpain2 in ZBTB18 regulation in Glioblastoma Multiforme

Hochschulschrift

Abstract: Glioblastoma multiforme (GBM) is the most common and aggressive form of primary human brain tumor. Despite the current comprehensive treatments, patients’ survival remains poor. Recent advances in molecular profiling reveal the distinct gene expression signatures that could further classify GBMs to prognosis-relevant subtypes, in which the Mesenchymal form represents the most lethal features.
Previously, we have identified ZBTB18 (Zinc finger and BTB domain-containing protein 18) as a transcriptional repressor in Mesenchymal transformation and epithelial-mesenchymal transition (EMT) in GBMs. Interestingly, a truncated form of ZBTB18 is also tumor-specifically observed in brain tumor stem-like cells (BTSCs), indicating a hypothesis that GBM progression is promoted upon the loss of intactness of ZBTB18. The present study first validates the characteristics of the cleaved ZBTB18, including its abnormal localization and the loss of transcriptional regulation.
By Microarray analysis for protease-encoding genes, we detect Calpain2 as the putative protease which is associated with cleaved ZBTB18 expression in BTSCs. By interfering with its activity or modulating its expression, we further identify the regulatory role of Calpain2 in ZBTB18 cleavage. In addition, one critical site for Calpain2 recognition is validated at Arg266-Ser267, while the cleavage site locates between Asn268 and Leu269 of ZBTB18. Therefore, it suggests that Calpain2 intervention could be developed as a potential therapeutic strategy for restoring ZBTB18 function in GBMs

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2019

Classification and Topics

• Keyword: Glioblastoma multiforme ; Glioblastom ; Zink-Finger-Proteine ; Calpaine ; Proteasen

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Yuan, Shuai
• Contributor: Carro, Maria Stella ; Niedermann, Gabriele ; Carro, Maria Stella ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Further information

• DOI: 10.6094/UNIFR/155345
• URN: urn:nbn:de:bsz:25-freidok-1553451
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:50 PM CET