TRIB1 (tribbles pseudokinase 1)

Johnston, Jessica; Kiss-Tóth, Endre

doi:10.4267/2042/62523

Cited by 1 publication

(1 citation statement)

References 12 publications

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“…The structure of TRIB1 is composed of three domains: The N-terminal domain (AA 1-90), the central pseudokinase domain (AA 91-330), and the C-terminal domain (AA 331-373) [19,20]. The N-terminal domain of TRIB1 contains a putative nuclear localization signal spanning residues 33-51, which is shown to be required for nuclear localization [9].…”

Section: Evolution and Structure Of Trib1mentioning

confidence: 99%

“Oh, Dear We Are in Tribble”: An Overview of the Oncogenic Functions of Tribbles 1

Singh,

Showalter,

Manring

et al. 2024

Cancers

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Pseudokinases are catalytically inactive proteins in the human genome that lack the ability to transfer phosphate from ATP to their substrates. The Tribbles family of pseudokinases contains three members: Tribbles 1, 2, and 3. Tribbles 1 has recently gained importance because of its involvement in various diseases, including cancer. It acts as a scaffolding protein that brings about the degradation of its substrate proteins, such as C/EBPα/β, MLXIPL, and RAR/RXRα, among others, via the ubiquitin proteasome system. It also serves as an adapter protein, which sequesters different protein molecules and activates their downstream signaling, leading to processes, such as cell survival, cell proliferation, and lipid metabolism. It has been implicated in cancers such as AML, prostate cancer, breast cancer, CRC, HCC, and glioma, where it activates oncogenic signaling pathways such as PI3K-AKT and MAPK and inhibits the anti-tumor function of p53. TRIB1 also causes treatment resistance in cancers such as NSCLC, breast cancer, glioma, and promyelocytic leukemia. All these effects make TRIB1 a potential drug target. However, the lack of a catalytic domain renders TRIB1 “undruggable”, but knowledge about its structure, conformational changes during substrate binding, and substrate binding sites provides an opportunity to design small-molecule inhibitors against specific TRIB1 interactions.

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Section: Evolution and Structure Of Trib1mentioning

confidence: 99%