Investigation of the pseudokinase TRIB2 : a double-edged sword in AML

• Main Author: Salomè, Mara
• Published: University of Glasgow 2017
• Subjects: 616.99; QH301 Biology
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.726730

TRIB2 belongs to the TRIBBLES family of serine/threonine pseudokinases (TRIB1, TRIB2 and TRIB3). TRIBBLES regulate proliferation, survival, differentiation, metabolism and stress responses, and their expression is frequently deregulated in cancer, including Acute myeloid leukaemia (AML). AML is a heterogeneous group of blood malignancies characterised by differentiation block and uncontrolled proliferation of myeloid precursor cells. Aberrant TRIB2 expression drives myeloid transformation through downregulation of the tumour suppressor CCAAT/enhancer-binding protein (C/EBPα). However, the mechanism of TRIB2 gene deregulation in cancer, and the role of TRIB2 in the oncogenic pathways of other AML oncogenes have not been fully investigated. Moreover, there is still limited information regarding the expression and function of TRIB2 and its family members, in the haemopoietic system, and how this is altered in different AML subtypes. This work aims to address these biological questions, by employing in silico, in vitro and in vivo experimental strategies.