Trib2 regulates the pluripotency of embryonic stem cells and enhances reprogramming efficiency

Abstract

Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process.

LncRNA XIST promotes the progression of laryngeal squamous cell carcinoma via sponging miR-125b-5p to modulate TRIB2

“…These data indicated that the promotive action of XIST to LSCC progression exerted through directly bating miR-125b-5p expression. Tribbles homolog 2 (TRIB2) belongs to Tribbles pseudokinases, playing a pivotal role in etiology of multifarious cancers [26,27]. Investigators found TRIB2 expression was elevated in colorectal cancer (CRC) and TRIB2 overexpression promoted cell proliferation and deferred cellular senescence of CRC partially relying on direct regulation of p21 expression and transcription factor AP4 expression [28].…”

miR-509-5p Inhibits the Proliferation and Invasion of Osteosarcoma by Targeting TRIB2

“…As a member of the tribble family, tribbles homolog 2 (TRIB2) is a mitosis blocker that regulates embryo and germ cell development [18]. It has been reported that, as a scaffold protein [19], TRIB2 plays a critical role in various biological processes as well as in pathological conditions, especially in tumor development [20,21]. For instance, the overexpression of TRIB2 may accelerate the acute myeloid leukemia (AML) through activating C/EBPα pathway [22]; in liver cancer, TRIB2 promoted cell proliferation and transformation via improving the stabilization of YAP through the E3 ubiquitin ligase βTrCP [23].…”

TRIB2 functions as novel oncogene in colorectal cancer by blocking cellular senescence through AP4/p21 signaling

“…It comprises an N-terminal domain, a C-terminal domain, and a central pseudokinase domain that contains a Ser/Thr protein kinase-like domain but lacks ATP affinity and catalytic activity [2]. In the absence of kinase activity, TRIB2 functions as a scaffold protein to regulate different signaling pathway in fundamental biological processes as well as in pathological conditions, including cancer [3]. TRIB2 plays a crucial role in regulating various cellular processes in cancer, such as proliferation, apoptosis and drug resistance [4–6].…”