Ubiquitination and adaptive responses to BRAF inhibitors in Melanoma

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

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Additional information

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.