TRIB2 Regulates Normal and Stress-induced Thymocyte Proliferation

Overview

Journal Cell Discov

Date 2016 Jul 28

PMID 27462446

Citations 22

Authors

Kai Ling Liang

Caitriona OConnor

J Pedro Veiga

Tommie V McCarthy

Karen Keeshan

Affiliations

Soon will be listed here.

Abstract

TRIB2, a serine/threonine pseudokinase identified as an oncogene, is expressed at high levels in the T-cell compartment of hematopoiesis. The proliferation of developing thymocytes is tightly controlled to prevent leukemic transformation of T cells. Here we examine Trib2 loss in murine hematopoiesis under steady state and proliferative stress conditions, including genotoxic and oncogenic stress. Trib2 (-/-) developing thymocytes show increased proliferation, and Trib2 (-/-) mice have significantly higher thymic cellularity at steady state. During stress hematopoiesis, Trib2 (-/-) developing thymocytes undergo accelerated proliferation and demonstrate hypersensitivity to 5-fluorouracil (5-FU)-induced cell death. Despite the increased cell death post 5-FU-induced proliferative stress, Trib2 (-/-) mice exhibit accelerated thymopoietic recovery post treatment due to increased cell division kinetics of developing thymocytes. The increased proliferation in Trib2 (-/-) thymocytes was exacerbated under oncogenic stress. In an experimental murine T-cell acute lymphoblastic leukemia (T-ALL) model, Trib2 (-/-) mice had reduced latency in vivo, which associated with impaired MAP kinase (MAPK) activation. High and low expression levels of Trib2 correlate with immature and mature subtypes of human T-ALL, respectively, and associate with MAPK. Thus, TRIB2 emerges as a novel regulator of thymocyte cellular proliferation, important for the thymopoietic response to genotoxic and oncogenic stress, and possessing tumor suppressor function.

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