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Reactivating p53 functions by suppressing its novel inhibitor iASPP : a potential therapeutic opportunity in p53 wild-type tumors


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タイトル: Reactivating p53 functions by suppressing its novel inhibitor iASPP : a potential therapeutic opportunity in p53 wild-type tumors
著者: Dong, Peixin 著作を一覧する
Ihira, Kei 著作を一覧する
Hamada, Junichi 著作を一覧する
Watari, Hidemichi 著作を一覧する
Yamada, Takahiro 著作を一覧する
Hosaka, Masayoshi 著作を一覧する
Hanley, Sharon J. B. 著作を一覧する
Kudo, Masataka 著作を一覧する
Sakuragi, Noriaki 著作を一覧する
キーワード: review
reactivation of p53
発行日: 2015年 7月13日
出版者: Impact Journals
誌名: Oncotarget
巻: 6
号: 24
開始ページ: 19968
終了ページ: 19975
出版社 DOI: 10.18632/oncotarget.4847
抄録: Although mutational inactivation of p53 is found in 50% of all human tumors, a subset of tumors display defective p53 function, but retain wild-type (WT) p53. Here, direct and indirect mechanisms leading to the loss of WT p53 activities are discussed. We summarize the oncogenic roles of iASPP, an inhibitor of WT p53, in promoting proliferation, invasion, drug or radiation-resistance and metastasis. From the therapeutic view, we highlight promising perspectives of microRNA-124, peptide and small molecules that reduce or block iASPP for the treatment of cancer. High iASPP expression enhances proliferation, aggressive behavior, the resistance to radiation/chemotherapy and correlates with poor prognosis in a range of human tumors. Overexpression of iASPP accelerates tumorigenesis and invasion through p53-dependent and p53-independent mechanisms. MicroRNA-124 directly targets iASPP and represses the growth and invasiveness of cancer cells. The disruption of iASPP-p53 interaction by a p53-derived peptide A34 restores p53 function in cancer cells. The inhibition of iASPP phosphorylation with small molecules induces p53-dependent apoptosis and growth suppression. The mechanisms underlying aberrant expression of iASPP in human tumors should be further investigated. Reactivating WT p53 functions by targeting its novel inhibitor iASPP holds promise for potential therapeutic interventions in the treatment of WT p53-containing tumors.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 董 培新


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