平成 25 年 6 月 19 日
June/19/2013
大学院学生各位
To All Graduate Students
平成 25 年度
基盤医学特論
特徴あるプログラム【Cancer Science Course】
開講通知
Information on Special Lecture Tokuron 2013
Toku Pro2013
題目：Keap1-Nrf2 制御系によるストレス応答と代謝リプログラミング
Title： Redox homeostasis and metabolic reprogramming in cancer cells by the Keap1-Nrf2
pathway
講師：本橋ほづみ
先生
（東北大学加齢医学研究所
加齢制御部門
遺伝子発現制御分野
教授）
Teaching Staff :Hozumi Motohashi MD. Ph.D, Professor,
Institute of Development, Aging and Caner, Tohoku University
日時：平成 25 年 7 月 2 日（火曜日）17 時 00 分～18 時 30 分
Time and Date: July 2, 2013 (Tue) 17:00-18:30
場所： 基礎研究棟
会議室２（生協印刷部隣）
Room : Building for Medical Research Meeting Room 2
言語： 英語
Language:
English
※ 関係講座・部門等の連絡担当者 分子腫瘍学
荒川（内線 2454）
Contact : Division of Molecular Carcinogenesis
Arakawa (ext 2454)
**事前申し込み不要です。No registration required.
医学部学務課大学院掛
Student Affairs Division, School of Medicine
Abstract：
Redox homeostasis and metabolic reprogramming in cancer cells by the
Keap1-Nrf2 pathway
Hozumi Motohashi
Institute of Development, Aging and Cancer, Tohoku University
Nrf2 is a master transcriptional activator of genes encoding cytoprotective
enzymes and antioxidant proteins that are induced in response to
electrophiles and reactive oxygen species (ROS) of exogenous and
endogenous origins. Under unstressed conditions, Nrf2 is constantly
ubiquitinated by Keap1 and degraded in the proteasome. During
exposure to electrophiles or ROS, Keap1 is inactivated, and Nrf2 is
stabilized.
Consequently, Nrf2 activates transcription, conferring
resistance against xenobiotic and oxidative stress.
Constitutive
stabilization of Nrf2 has been observed in substantial numbers of human
cancers for genetic and/or epigenetic reasons. Cancers with increased
levels of Nrf2 are associated with poor prognosis because of not only
resistance against chemotherapy and radiotherapy but also aggressive
proliferation. We recently found that Nrf2 accelerates cell proliferation
through directly activating the pentose phosphate pathway and
simultaneously facilitating purine nucleotide synthesis and glutamine
metabolism in the presence of proliferative signals. The activation of
PI3K-Akt signaling enables Nrf2 to induce these metabolic genes, which
contributes to the establishment of metabolic activities unique to cancer
cells. The functional potentiation of Nrf2 by proliferative signals boosts
the reorganization of cellular metabolic activities supporting cell
proliferation. Dual role of Nrf2 in the stress response and metabolic
reprogramming underlies the malignant evolution of cancers.