DUX4-r exerts a neomorphic activity that depends on GTF2I in acute lymphoblastic leukemia.

Translocations producing rearranged versions of the transcription factor double homeobox 4 (DUX4-r) are one of the most frequent causes of B cell acute lymphoblastic leukemia (B-ALL). DUX4-r retains the DNA binding domain of wild-type DUX4 but is truncated on the C-terminal transcription activation domain. The precise mechanism through which DUX4-r causes leukemia is unknown, and no targeted therapy is currently available.

Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant hemopoiesis.

TRIBBLES pseudokinases (TRIB1, TRIB2, and TRIB3) are important regulators of normal and malignant hemopoiesis. The relative abundance of each TRIBBLES family member may be important for distinct oncogenic or tumor suppressor functions. We map the expression profiles of TRIB1, TRIB2, and TRIB3 in human and murine hemopoietic stem, progenitor and mature cells, and in human leukemia datasets.

A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling.

Trib2 pseudokinase is involved in the etiology of a number of cancers including leukaemia, melanoma, ovarian, lung and liver cancer. Both high and low Trib2 expression levels correlate with different types of cancer. Elevated Trib2 expression has oncogenic properties in both leukaemia and lung cancer dependent on interactions with proteasome machinery proteins and degradation of transcription factors.

Trib2 expression in granulocyte-monocyte progenitors drives a highly drug resistant acute myeloid leukaemia linked to elevated Bcl2.

Trib2 pseudokinase has oncogenic and tumour suppressive functions depending on the cellular context. We investigated the ability of Trib2 to transform different haemopoietic stem and progenitor cells (HSPCs). Our study identified the granulocyte-macrophage progenitor (GMP) subpopulation as a potent leukaemia initiating cell of Trib2-driven AML .

TRIB2 and the ubiquitin proteasome system in cancer.

Tribbles family of pseudokinase proteins are known to mediate the degradation of target proteins in Drosophila and mammalian systems. The main protein proteolysis pathway in eukaryotic cells is the ubiquitin proteasome system (UPS). The tribbles homolog 2 (TRIB2) mammalian family member has been well characterized for its role in murine and human leukaemia, lung and liver cancer.

Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival.