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Oncoprotein stabilization in brain tumors

Oncogene volume 33, pages 4709–4721 (2014)Cite this article

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Abstract

Proteins involved in promoting cell proliferation and viability need to be timely expressed and carefully controlled for the proper development of the brain but also efficiently degraded in order to prevent cells from becoming brain cancer cells. A major pathway for targeted protein degradation in cells is the ubiquitin–proteasome system (UPS). Oncoproteins that drive tumor development and tumor maintenance are often deregulated and stabilized in malignant cells. This can occur when oncoproteins escape degradation by the UPS because of mutations in either the oncoprotein itself or in the UPS components responsible for recognition and ubiquitylation of the oncoprotein. As the pathogenic accumulation of an oncoprotein can lead to effectively sustained cell growth, viability and tumor progression, it is an indisputable target for cancer treatment. The most common types of malignant brain tumors in children and adults are medulloblastoma and glioma, respectively. Here, we review different ways of how deregulated proteolysis of oncoproteins involved in major signaling cancer pathways contributes to medulloblastoma and glioma development. We also describe means of targeting relevant oncoproteins in brain tumors with treatments affecting their stability or therapeutic strategies directed against the UPS itself.

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Acknowledgements

This work was supported by research from the Swedish Childhood Cancer Foundation (FJS, OS), the Swedish Cancer Society (FJS, OS), the Swedish Research Council (FJS, OS), the Swedish Society of Medicine (FJS), the Swedish Brain Foundation (FJS), Ã…ke Wibergs stiftelse (FJS), Ã…ke Olssons Stiftelse (OS), Lions Cancerforskningsfond (FJS), Stiftelsen Lars Hiertas Minne (FJS), Radiumhemmets Forskningsfonder (OS), Karolinska Institute Foundations (OS) and the Association for International Cancer Research (FJS). We apologize to authors not cited due to space restrictions in this review.

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  1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    S-M Hede, V Savov, H Weishaupt & F J Swartling

  2. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

    O Sangfelt

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Hede, SM., Savov, V., Weishaupt, H. et al. Oncoprotein stabilization in brain tumors. Oncogene 33, 4709–4721 (2014). https://doi.org/10.1038/onc.2013.445

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