Investigating molecular mechanisms of TRAF7 mutations identified by genome-wide analysis

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2017

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Gülez, Burcu

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Meningiomas are defined as the most common primary intracanial neoplasms which originate from meninges. Recent genomic studies identified critical driver mutations in several genes including TRAF7 (TNF Receptor-Associated Factor 7) . Previously, studies performed in Prof. Gunel’s laboratory suggested that mutant forms of TRAF7 protein were more stable, possibly due to change in their ubiquitination level. To begin understanding the underlying mechanisms, we looked into interaction partners of TRAF7. TRAF7 is known to interact with TRAF4 (TNF Receptor-Associated Factor 4) and TRAF6 (TNF Receptor-Associated Factor 6). We show that the binding affinity of TRAF7 G536S mutant to TRAF4 was lower compared to other TRAF7 mutants and TRAF7 wild type. However, the interaction between TRAF7 mutants and TRAF6 was not significantly different than that of wild type TRAF7. In addition, we showed lower ubiquitination of K27 and K29 sites on TRAF7 mutants compared to the wild type TRAF7. Interestingly, ubiquitination level on K63 site of mutant TRAF7 wa not significantly altered. Given that TRAF4 and TRAF6 have ubiquitin ligse functions, we think it may be possible that TRAF4 is responsible for K27 and K29 ubiquitination whereas TRAF6 ubiquitinates K63 of TRAF7. Future studies investigating detailed mechanism of TRAF7 ubiquitination by its interacting partners may help to better understand meningioma and to discover novel therapeutic targets to treat this challenging disease.

Subject Keywords

Meningioma., Brain, Molecular genetics.

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http://etd.lib.metu.edu.tr/upload/12621671/index.pdf
https://hdl.handle.net/11511/26884

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

B. Gülez, “Investigating molecular mechanisms of TRAF7 mutations identified by genome-wide analysis,” M.S. - Master of Science, Middle East Technical University, 2017.