TRIB2 and the ubiquitin proteasome system in cancer

Salomé, Mara; Campos, Joana; Keeshan, Karen

doi:10.1042/bst20150103

Cited by 20 publications

(19 citation statements)

References 48 publications

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“…Interestingly, the broad analysis of all cancers failed to identify conserved mutations or chromosomal alterations involving TRIB2. By contrast, its elevated expression is strongly associated with cancer prognostics [77]. Indeed, TRIB2 has been identified as a candidate biomarker for melanoma diagnosis and progression, because it exhibits low expression in healthy skin samples, increases in benign melanoma, with the highest expression seen in malignant melanoma samples [78].…”

Section: Trib Pseudokinase Functions In Other Model Cancer Systemsmentioning

confidence: 99%

Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease

Eyers

Keeshan

Kannan

2017

Trends in Cell Biology

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183

207

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The Tribbles (TRIB) pseudokinases control multiple aspects of eukaryotic cell biology and evolved unique features distinguishing them from all other protein kinases. The atypical pseudokinase domain retains a regulated binding platform for substrates, which are ubiquitinated by context-specific E3 ligases. This plastic configuration has also been exploited as a scaffold to support the modulation of canonical MAPK and AKT modules. In this review, we discuss the evolution of TRIBs and their roles in vertebrate cell biology. TRIB2 is the most ancestral member of the family, whereas the emergence of TRIB3 homologs in mammals supports additional biological roles, many of which are currently being dissected. Given their pleiotropic role in diseases, the unusual TRIB pseudokinase conformation provides a highly attractive opportunity for drug design.

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Section: Trib Pseudokinase Functions In Other Model Cancer Systemsmentioning

confidence: 99%

Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease

Eyers

Keeshan

Kannan

2017

Trends in Cell Biology

Self Cite

183

207

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“…HCT 116 or SW 480 stable cell lines were seeded in 96-well plates at a density of 8000 cells/well. At five time points (12,24,48,60, and 72 hours), Cell Counting Kit-8(CCK-8) solution(Dojindo Molecular Technology Inc, Shanghai, China) was used to detect cells growth. The absorbance at 450 nm was measured by an automatic microplate reader.…”

Section: Cck8 Assaymentioning

confidence: 99%

“…CHIP has been known as an E3 ubiquitin ligase, which could degradate many oncoproteins and tumor suppressor protein by ubiquitination in cancers [10]. There are Ivyspring International Publisher more and more studies on the role of ubiquitinproteasome pathway in tumors [11][12][13]. Every link of ubiquitination maybe become tumor target, which could offer a better method to prdict cancer prognosis or treat cancer.…”

Section: Introductionmentioning

confidence: 99%

CHIP-mediated ubiquitination of Galectin-1 predicts colorectal cancer prognosis

et al. 2020

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CHIP and Galectin-1 are associated with the development of metastasis in cancer. However, the precise roles of CHIP or Gal1 in colorectal cancer are uncertain. Here, our study explored the relationship and clinical significance of CHIP or Gal1 in CRC. CHIP or Gal1 expression was significantly decreased or up-regulated in CRC compared with adjacent noncancerous tissues by immunohistochemistry on a CRC tissue microarray, respectively. Low CHIP or high Gal1 expression significantly correlated with clinicopathological characteristics in patients, as well as with shorter overall survival. Multivariate Cox regression analysis revealed that CHIP or Gal1 expression was an independent prognostic factor for CRC patients. Moreover, CHIP associated with Gal1 has a synergistic effect on the prediction of CRC prognosis. In vitro and vivo, high CHIP or low Gal1 expression inhibit CRC growth or metastasis. Our results found that CHIP could degradate Gal1 by ubiquitination. In summary, CHIP could inhibit CRC growth or metastasis through promoting Gal1 ubiquitination and degradation by proteasome. CHIP and Gal1 expressions are novel candidate prognostic markers in CRC. A combined effect of CHIP and Gal1 as efficient prognostic indicators was found for the first time.

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“…alpha, beta, delta (α, β and δ) play crucial roles in lineage specific differentiation of endothelial, smooth muscle and adipose cells [76][77][78]. These C/EBP proteins are also well-known regulators of cancer cell growth [79,80]. Indeed, Bowers et al (2002) was the first to show that the mammalian tribbles homolog, TRIB3 (a.k.a.…”

Section: The Multifunctional Tribblesmentioning

confidence: 99%

Tripping on TRIB3 at the junction of health, metabolic dysfunction and cancer

2016

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Metabolic diseases like obesity, atherosclerosis and diabetes are frequently associated with increased risk of aggressive cancers. Although metabolic dysfunctions in normal cells are manifested due to defective signaling networks that control cellular homeostasis, malignant cells utilize these signaling networks for their increased survival, growth and metastasis. Despite decades of research, a common mechanistic link between these chronic pathologies is still not well delineated. Evidences show that the unfolded protein response (UPR) and the endoplasmic reticulum stress (ERS) pathways are often dysregulated in both metabolic diseases and cancer. The UPR also triggers coordinated signaling with both PI3K/AKT/mTOR and Autophagy pathways in order to promote stress-adaptive mechanisms. Whereas, uncontrolled UPR and the resultant ERS escalates cells towards metabolic dysfunctions and ultimately cell death. In this review, we will discuss findings that implicate a crucial role for the multifunctional ERS-induced protein, TRIB3. The 'pseudokinase' function of TRIB3 facilitates the inactivation of multiple transcription factors and signaling proteins. The MEK1 binding domain of TRIB3 enables it to deactivate multiple MAP-kinases. In addition, the COP1 motif of TRIB3 assists ubiquitination and proteasomal degradation of numerous TRIB3 associated proteins. The most well studied action of TRIB3 has been on the PI3K/AKT/mTOR pathway, where TRIB3-mediated inhibition of AKT phosphorylation decreases insulin signaling and cell survival. Conversely, cancer cells can either upregulate the AKT survival pathway by suppressing TRIB3 expression or alter TRIB3 localization to degrade differentiation inducing nuclear transcription factors such as C/EBPα and PPARγ. The gain-of-function Q84R polymorphism in TRIB3 is associated with increased risk of diabetes and atherosclerosis. TRIB3 acts as a crucial 'stress adjusting switch' that links homeostasis, metabolic disease and cancer; and is being actively investigated as a disease biomarker and therapeutic target.

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TRIB2 and the ubiquitin proteasome system in cancer

Cited by 20 publications

References 48 publications

Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease

Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease

CHIP-mediated ubiquitination of Galectin-1 predicts colorectal cancer prognosis

Tripping on TRIB3 at the junction of health, metabolic dysfunction and cancer

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