Abstract
Simple SummaryTRIB1 is at the center of major cell signaling pathways. In this review, we describe its role in immune cells and highlight TRIB1 interacting partners which suggests cell-specific functions and that TRIB1 is involved in cellular homeostasis and also in different cancers and immune-related disorders.Research advances in Tribbles homolog (TRIB) genes have established the consensus that this protein family plays roles in diverse biological conditions and regulates intracellular signaling networks and several human diseases. In this review, we focus on one member of the family, TRIB1, and its role at the crossroads of immune signaling. TRIB1 directly interacts with transcription factors such as FOXP3 and C/EBPα, with several signaling molecules such as MEK1 and MALT1 and directly acts on key cell signaling pathways such as the MAPK and NF-κB pathways. Altogether, these interactions emphasize that TRIB1 is at the center of major cell signaling pathways while TRIB1 has cell-specific roles, potentially depending on the expressing cells and binding partners. In this review, we describe its roles in immune cells and highlight the interacting partners explaining these functions which suggests TRIB1 as a precise mediator of cellular homeostasis as well as in different cancers and immune-related disorders.
Highlights
Tribbles homolog (TRIB) gene characterization dates back to 1996 when Wilkin et al.identified a member of the Tribbles protein family differentially expressed in the dog thyroid gland [1]
By determining the crystal structure of TRIB1, Murphy et al evidenced that the C-terminal domain domain of TRIB1 binds with constitutive photomorphogenesis protein-1 (COP1), forming the ubiquitin ligase complex, which binds to its substrate C/EBPα [18]
This study examined the sensitivity of the TRIB1 protein to alterations in translational and transcriptional activity using cell lines, showing that inhibiting translation using cycloheximide (CHX) resulted in a significant reduction in the TRIB1 protein level (>70%), while inhibiting transcription using ACTD resulted in a 30–40% decrease in its protein level
Summary
Tribbles homolog (TRIB) gene characterization dates back to 1996 when Wilkin et al. identified a member of the Tribbles protein family differentially expressed in the dog thyroid gland [1]. Tribbles was determined to act by negatively regulating the cell cycle regulator String/Cdc, supporting its suppression of expression, allowing the gastrulation phase to take place and delaying the initiation of mitosis [3,4]. These early studies highlighted essential hallmarks of TRIB protein family members, with specific roles of TRIBs in specific developmental stages [2,3], in modulating specific protein targets [3,5], and having cell-specific roles [6]. TRIB1 roles are guided through interacting partners that confer cell-specific functions, notably in immune cells, the focus of this review
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