GSKIP (GSK3-beta interaction protein)

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Title: GSKIP (GSK3-beta interaction protein)
Author: Bellanné-Chantelot, Christine; Plo, Isabelle
Abstract: GSK3beta interaction protein (GSKIP) is a negative regulator of GSK3B (GSK3 beta) which is a highly conserved serine-threonine kinase involved in many cellular processes including glycogen metabolism, proliferation, differentiation, and development. GSKIP directly interacts with GSK3B through its C-terminal conserved GSK3B -binding domain (GID) and negatively regulates GSK3B in the Wnt/ beta -catenin signaling pathway. The overexpression of GSKIP may result in the activation of the Wnt pathway involved in hematopoietic stem cell homeostasis and normal megakaryopoiesis and in the development of leukemia stem cells in acute myeloid leukemia (AML). In a mouse model, GSK3B allelic deletion results in a myelodysplastic syndrome that, when combined with GSK3A deletion, leads to AML The germline duplication of ATG2B and GSKIP, both located in 14q32.2, predisposes to the development of familial myeloproliferative neoplasms with autosomal dominant inheritance, in particular essential thrombocythemia progressing to leukemia. Overexpression of ATG2B and GSKIP enhances megakaryocyte progenitor differentiation by increasing progenitor sensitivity to thrombopoietin. Both genes cooperate with somatic JAK2, MPL and CALR mutations and their overexpression provides a growth advantage to hematopoietic cells carrying these driver mutations that may explain the familial aggregation and the progression of essential thrombocythemia to myelofibrosis and leukemia.
Subject: GSKIP; Myeloproliferative neoplasms (MPN); essential thrombocythemia; myelofibrosis; leukemia; predisposition; ATG2B/GSKIP; chromosome 14; CNV; autophagy; Wnt/beta-catenin pathway; Genes Section; Animals; Disease Models, Animal; Glycogen Synthase Kinase 3/deficiency/*metabolism; Glycogen Synthase Kinase 3 beta; Hematopoietic Stem Cells/*enzymology; Humans; Leukemia, Myeloid, Acute/*enzymology/genetics/therapy; Mice, Transgenic; Proto-Oncogene Proteins c-akt/metabolism; Signal Transduction/physiology; Adolescent; Adult; Aged; Autophagy-Related Proteins
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2017

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