東北大学加齢医学研究所 加齢医学研究拠点 | Institute of Development, Aging and Cancer, Tohoku University

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◇平成28年5月18日(水)加齢研セミナ-のご案内
日時: 平成28年5月18日(水)午後5時~
場所: 加齢研実験研究棟7階 セミナー室1
演題: Disruption of redox signaling in cancer: the role of Nrf2 in cancer development
講師: Aikseng Ooi
所属: College of Pharmacy, University of Arizona
担当: 本橋 ほづみ(遺伝子発現制御分野・内線8550)
要旨: The NRF2 transcription factor is the main regulator of cellular redox balance. Upon activation NRF2 promotes the expression of genes involved in xenobiotic and energy metabolisms, which facilitate the removal of electrophiles and neutralization of radical oxygen species, thereby restoring cellular redox balance. NRF2 is primarily regulated through its interactions with a protein known as KEAP1 (Kelch-like ECH-associated protein 1), a substrate adaptor protein for a CUL3-dependent ubiquitin ligase complex that ubiquitylates NRF2 for degradation. KEAP1 serves as a cellular electrophile sensor, whereby its surface cysteine residues are amenable to covalent modifications by various electrophiles. These modifications prevent KEAP1 mediated NRF2 ubiquitylation, leading to the accumulation and activation of NRF2. NRF2 activation is canonically accepted as a protection mechanism against malignant transformation. However recent studies unveiled an overrepresentation of somatic gain-of-function NRF2 mutations and somatic loss-of-function KEAP1 mutations in various cancer types. Collectively, these mutations drive a sustained NRF2 activation phenotype, suggesting that NRF2 activation may play a role in cancer development and progression. We provide a data-driven model of the role of NRF2 activation in carcinogenesis in both hereditary and sporadic cancers.


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