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Gene of the month: BRAF
  1. Dhirendra Govender1,
  2. Runjan Chetty2
  1. 1Division of Anatomical Pathology, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa
  2. 2Department of Cellular Pathology and Nuffield Department of Clinical Laboratory Sciences, Oxford Biomedical Research Centre, Oxford University Hospitals Trust and University of Oxford University, Oxford, UK
  1. Correspondence to Professor Dhirendra Govender, Division of Anatomical Pathology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa; Dhiren.Govender{at}uct.ac.za

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Second RAF paralogue (BRAF) is a proto-oncogene that encodes a serine/threonine kinase that transduces regulatory signals through the Rat Sarcoma (RAS)/RAF/ mitogen-activated protein kinase extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. This pathway is hyperactivated in approximately 30% of human cancers.1 Activating mutations in the RAS oncogenes occur in 15%–30% of cancers.2 Kirsten murine sarcoma virus oncogene (KRAS) is an important and frequently mutated member of this group of oncogenes. Gain-of-function BRAF mutations results in aberrant activation of ERK signalling that is involved in several cancers such as thyroid papillary carcinoma, melanoma and colon carcinoma mainly but also as demonstrated in animal models in ovarian, skin, lung cancers and glioblastoma multiforme.3 ,4

Structure

There are three related RAF genes in mammals: first RAF paralogue (ARAF), BRAF and human homologue of v-RAF (CRAF) (RAF-1). The BRAF gene, located at 7q34, contains 18 exons and encodes a serine–threonine kinase in the RAS/RAF/MAPK signalling pathway.5 All the main RAF proteins share three highly conserved regions: CR1, CR2 and CR3; however, BRAF has a number of structural differences from the other RAF proteins (ARAF and CRAF). CR1 contains the RAS binding domain and the cysteine-rich domain.6–10 CR2 is rich in serine and threonine and contains regulatory phosphorylation sites. CR3 contains the P-loop and the important kinase …

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