Ubiquitination and adaptive responses to BRAF inhibitors in Melanoma

Azad Saei; Pieter Johan Adam Eichhorn

doi:10.1080/23723556.2018.1497862

Ubiquitination and adaptive responses to BRAF inhibitors in Melanoma

Mol Cell Oncol. 2018 Sep 5;5(5):e1497862. doi: 10.1080/23723556.2018.1497862. eCollection 2018.

Authors

Azad Saei^{1

2}, Pieter Johan Adam Eichhorn^{3

4

5}

Affiliations

¹ Genome Institute of Singapore, ASTAR, Singapore.
² Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³ Cancer Science Institute of Singapore, National University of Singapore, Singapore.
⁴ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁵ School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Australia.

Abstract

Response to targeted therapies is limited by the activation or inhibition of feedback loops. Here we report the ubiquitin specific peptidase 28/F-box WD repeat-containing protein 7 (USP28/FBW7) complex functions as a negative regulator of mitogen-activated protein kinase (MAPK) pathway by targeting v-raf murine sarcoma viral oncogene homolog B (BRAF) for degradation, a process which is lost in a large proportion of BRAF mutant melanoma patients, resulting in resistance to BRAF inhibitor therapies.

Keywords: USP28/BRAF/Melanoma/Vemurafenib resistance.

Grants and funding

This work was in part supported by the by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative.