Nucleoporin TPR (Translocated Promoter Region, Nuc;ear Basket Protein) Upregulation Alters MTOR-HSF1 Trails adn Suppresses Autophagy Induction in Ependymoma

Dewi, Firli Rahma Primula and Jiapaer, Shabierjiang and Kobayashi, Akiko and Hazawa, Masaharu and Ikliptikawati, Dini Kurnia and Hartono, Hartono and Sabit, Hemragul and Nakada, Mitsutoshi and Wong, Richard W (2021) Nucleoporin TPR (Translocated Promoter Region, Nuc;ear Basket Protein) Upregulation Alters MTOR-HSF1 Trails adn Suppresses Autophagy Induction in Ependymoma. Autophagy, 17 (4). pp. 1001-1012.

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Official URL: https://pubmed.ncbi.nlm.nih.gov/32207633/

Abstract

Children with ependymoma have high mortality rates because ependymoma is resistant to conventional theraphy. Genomic and transptomic studies have identified potential targets as significantly altered reported, the detailed mechanisms for the roles of these candidate oncogenes in ependymoma progression remain unclear. Here, we report an oncogenic role of the nucleoporin TPR (Translocated promoter region, nuclear basket protein) in regulating HSF1 (Heat Shock Transcription Factor 1) mRNA trafficking, maintaining MTORC1 activity to phosphorylate ULK1, and praventing macroautophagy/autophagy induction in ependymoma. High expression of TPR were associates with inreased HSF1 and HSPA/HSP70 expression in ependymoma patients. In an ependymoma mouse xenohraft model, MTOR inhibition by rapamycin therapeutically suppressed TPR expression and reduced tumor size in vivo. Togetherm these results suggest that TPR may act as a biomarker for ependymoma, and pharmacological interventions targeting TPR-HSF1-MTOR may have therapeutic potential for ependymoma treatment.

Item Type: Article
Subjects: FMIPA
Divisions: FAKULTAS MIPA
Depositing User: Zainatun
Date Deposited: 24 Jun 2023 01:28
Last Modified: 24 Jun 2023 01:28
URI: http://eprints.unm.ac.id/id/eprint/31214

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