Competition Between Members of the Tribbles Pseudokinase Protein Family Shapes Their Interactions with Mitogen Activated Protein Kinase Pathways

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 8

PMID 27600771

Citations 15

Authors

Hongtao Guan

Aban Shuaib

David Davila De Leon

Adrienn Angyal

Maria Salazar

Guillermo Velasco

Mike Holcombe

Steven K Dower

Endre Kiss-Toth

Affiliations

Soon will be listed here.

Abstract

Spatio-temporal regulation of intracellular signalling networks is key to normal cellular physiology; dysregulation of which leads to disease. The family of three mammalian tribbles proteins has emerged as an important controller of signalling via regulating the activity of mitogen activated protein kinases (MAPK), the PI3-kinase induced signalling network and E3 ubiquitin ligases. However, the importance of potential redundancy in the action of tribbles and how the differences in affinities for the various binding partners may influence signalling control is currently unclear. We report that tribbles proteins can bind to an overlapping set of MAPK-kinases (MAPKK) in live cells and dictate the localisation of the complexes. Binding studies in transfected cells reveal common regulatory mechanisms and suggest that tribbles and MAPKs may interact with MAPKKs in a competitive manner. Computational modelling of the impact of tribbles on MAPK activation suggests a high sensitivity of this system to changes in tribbles levels, highlighting that these proteins are ideally placed to control the dynamics and balance of activation of concurrent signalling pathways.

Citing Articles

The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo.

Hernandez-Quiles M, Martinez Campesino L, Morris I, Ilyas Z, Reynolds S, Tan N Mol Metab. 2024; 78:101829.

PMID: 38445671 PMC: 10663684. DOI: 10.1016/j.molmet.2023.101829.

Comprehensive Profiling of Mammalian Tribbles Interactomes Implicates TRIB3 in Gene Repression.

Hernandez-Quiles M, Baak R, Borgman A, den Haan S, Alcaraz P, van Es R Cancers (Basel). 2021; 13(24).

PMID: 34944947 PMC: 8699236. DOI: 10.3390/cancers13246318.

The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer.

Orea-Soufi A, Castillo-Lluva S, Salvador-Tormo N, Martin-Cabrera P, Recuero S, Gabicagogeascoa E Cancers (Basel). 2021; 13(21).

PMID: 34771470 PMC: 8582533. DOI: 10.3390/cancers13215307.

The Critical Role of TRIB2 in Cancer and Therapy Resistance.

Mayoral-Varo V, Jimenez L, Link W Cancers (Basel). 2021; 13(11).

PMID: 34070799 PMC: 8198994. DOI: 10.3390/cancers13112701.

Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila.

Dobens L, Nauman C, Fischer Z, Yao X Cancers (Basel). 2021; 13(4).

PMID: 33672471 PMC: 7923445. DOI: 10.3390/cancers13040883.

References

Stein S, Mack E, Rome K, Pear W . Tribbles in normal and malignant haematopoiesis. Biochem Soc Trans. 2015; 43(5):1112-5. PMC: 4613494. DOI: 10.1042/BST20150117. View

MacDonald M, Lamerdin J, Owens S, Keon B, Bilter G, Shang Z . Identifying off-target effects and hidden phenotypes of drugs in human cells. Nat Chem Biol. 2006; 2(6):329-37. DOI: 10.1038/nchembio790. View

Hegedus Z, Czibula A, Kiss-Toth E . Tribbles: novel regulators of cell function; evolutionary aspects. Cell Mol Life Sci. 2006; 63(14):1632-41. PMC: 11136108. DOI: 10.1007/s00018-006-6007-9. View

Salazar M, Lorente M, Garcia-Taboada E, Gomez E, Davila D, Zuniga-Garcia P . TRIB3 suppresses tumorigenesis by controlling mTORC2/AKT/FOXO signaling. Mol Cell Oncol. 2016; 2(3):e980134. PMC: 4905291. DOI: 10.4161/23723556.2014.980134. View

Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J . E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3. Cell Signal. 2008; 20(5):942-8. DOI: 10.1016/j.cellsig.2008.01.010. View

Yokoyama T, Kanno Y, Yamazaki Y, Takahara T, Miyata S, Nakamura T . Trib1 links the MEK1/ERK pathway in myeloid leukemogenesis. Blood. 2010; 116(15):2768-75. DOI: 10.1182/blood-2009-10-246264. View

Ashton-Chess J, Giral M, Mengel M, Renaudin K, Foucher Y, Gwinner W . Tribbles-1 as a novel biomarker of chronic antibody-mediated rejection. J Am Soc Nephrol. 2008; 19(6):1116-27. PMC: 2396937. DOI: 10.1681/ASN.2007101056. View

Zhang L, Zhang J, Liu X, Liu S, Tian J . Tribbles 3 regulates the fibrosis cytokine TGF- β 1 through ERK1/2-MAPK signaling pathway in diabetic nephropathy. J Immunol Res. 2014; 2014:240396. PMC: 4124808. DOI: 10.1155/2014/240396. View

Hua F, Li K, Yu J, Lv X, Yan J, Zhang X . TRB3 links insulin/IGF to tumour promotion by interacting with p62 and impeding autophagic/proteasomal degradations. Nat Commun. 2015; 6:7951. PMC: 4557121. DOI: 10.1038/ncomms8951. View

10.

Qi L, Heredia J, Altarejos J, Screaton R, Goebel N, Niessen S . TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science. 2006; 312(5781):1763-6. DOI: 10.1126/science.1123374. View

11.

Naiki T, Saijou E, Miyaoka Y, Sekine K, Miyajima A . TRB2, a mouse Tribbles ortholog, suppresses adipocyte differentiation by inhibiting AKT and C/EBPbeta. J Biol Chem. 2007; 282(33):24075-82. DOI: 10.1074/jbc.M701409200. View

12.

Sung H, Francis S, Crossman D, Kiss-Toth E . Regulation of expression and signalling modulator function of mammalian tribbles is cell-type specific. Immunol Lett. 2005; 104(1-2):171-7. DOI: 10.1016/j.imlet.2005.11.010. View

13.

Wei S, Rosenberg I, Cao Z, Huett A, Xavier R, Podolsky D . Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling. Inflamm Bowel Dis. 2012; 18(5):877-88. PMC: 3881418. DOI: 10.1002/ibd.22883. View

14.

Dugast E, Kiss-Toth E, Soulillou J, Brouard S, Ashton-Chess J . The Tribbles-1 protein in humans: roles and functions in health and disease. Curr Mol Med. 2012; 13(1):80-5. View

15.

Liang K, Rishi L, Keeshan K . Tribbles in acute leukemia. Blood. 2013; 121(21):4265-70. DOI: 10.1182/blood-2012-12-471300. View

16.

Remy I, Montmarquette A, Michnick S . PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nat Cell Biol. 2004; 6(4):358-65. DOI: 10.1038/ncb1113. View

17.

Remy I, Michnick S . Mapping biochemical networks with protein-fragment complementation assays. Methods Mol Biol. 2004; 261:411-26. DOI: 10.1385/1-59259-762-9:411. View

18.

Kiss-Toth E, Wyllie D, Holland K, Marsden L, Jozsa V, Oxley K . Functional mapping and identification of novel regulators for the Toll/Interleukin-1 signalling network by transcription expression cloning. Cell Signal. 2005; 18(2):202-14. DOI: 10.1016/j.cellsig.2005.04.012. View

19.

Sung H, Guan H, Czibula A, King A, Eder K, Heath E . Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways. J Biol Chem. 2007; 282(25):18379-18387. PMC: 2366084. DOI: 10.1074/jbc.M610792200. View

20.

Shuaib A, Hartwell A, Kiss-Toth E, Holcombe M . Multi-Compartmentalisation in the MAPK Signalling Pathway Contributes to the Emergence of Oscillatory Behaviour and to Ultrasensitivity. PLoS One. 2016; 11(5):e0156139. PMC: 4887093. DOI: 10.1371/journal.pone.0156139. View