Open Access

Ubiquitination of p21 by E3 ligase RNF135 promotes the proliferation of human glioblastoma cells

  • Authors:
    • Weiting Gu
    • Ming Wang
    • Zhebao Wu
    • Yu Cai
  • View Affiliations

  • Published online on: June 27, 2024     https://doi.org/10.3892/ol.2024.14539
  • Article Number: 406
  • Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma multiforme (GBM) is a highly heterogeneous tumor of the central nervous system with a high mortality rate. The upregulation of RING finger protein 135 (RNF135), an E3 ligase, has been observed in GBM, but the associated mechanisms have not been fully elucidated. The aim of the present study was to identify the substrate of RNF135 and study its functions in GBM. Bioinformatics analyses were performed. In addition, RNF135 was overexpressed or knocked down in human U87 and U251 GBM cells, and the effect on cell proliferation was analyzed using Cell Counting Kit‑8 and colony formation assays. Furthermore, the interaction of RNF135 with its potential substrate was analyzed using glutathione S‑transferase, yeast two‑hybrid, immunoprecipitation (IP), co‑IP and immunoblotting assays. Bioinformatics analysis indicated that RNF135 serves as a marker of poor prognosis in GBM. The overexpression of RNF135 was demonstrated to promote the proliferation of GBM cells, while the knockdown of RNF135 inhibited GBM cell growth. In addition, the results of the interaction experiments indicate that RNF135 interacts with p21 and mediates the degradation of p21 by ubiquitination. The major site of RNF135‑mediated p21 ubiquitination was identified as K163. Further experiments demonstrated that RNF135 promotes the proliferation of GBM cells mainly via p21. In summary, these findings suggest that RNF135 has potential as a therapeutic target for the treatment of GBM.
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September-2024
Volume 28 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Gu W, Wang M, Wu Z and Cai Y: Ubiquitination of p21 by E3 ligase RNF135 promotes the proliferation of human glioblastoma cells. Oncol Lett 28: 406, 2024.
APA
Gu, W., Wang, M., Wu, Z., & Cai, Y. (2024). Ubiquitination of p21 by E3 ligase RNF135 promotes the proliferation of human glioblastoma cells. Oncology Letters, 28, 406. https://doi.org/10.3892/ol.2024.14539
MLA
Gu, W., Wang, M., Wu, Z., Cai, Y."Ubiquitination of p21 by E3 ligase RNF135 promotes the proliferation of human glioblastoma cells". Oncology Letters 28.3 (2024): 406.
Chicago
Gu, W., Wang, M., Wu, Z., Cai, Y."Ubiquitination of p21 by E3 ligase RNF135 promotes the proliferation of human glioblastoma cells". Oncology Letters 28, no. 3 (2024): 406. https://doi.org/10.3892/ol.2024.14539