イツミ　モモエ   逸見　百江    所属   川崎医科大学  医学部 一般教養　自然科学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	A20 restores phorbol ester-induced differentiation of THP-1 cells in the absence of nuclear factor-κB activation.
掲載誌名	正式名：Journal of cellular biochemistry 略　 称：J Cell Biochem ISSNコード：10974644/07302312
掲載区分	国外
巻・号・頁	119(2),pp.1475-1487
著者・共著者	Miho Osako, Momoe Itsumi, Haruka Yamaguchi, Hiroaki Takeuchi, Shoji Yamaoka
発行年月	2018/02
概要	A20, also referred to as tumor necrosis factor alpha (TNFα)-induced protein 3 (TNFAIP3), is an ubiquitin-editing enzyme whose expression is enhanced by NF-κB activation, and plays an important role in silencing NF-κB activity. Another well-known role for A20 is to protect cells from TNFα-induced apoptosis. Depletion of NF-κB in differentiating U937 monocytic leukemia cells is known to cause apoptotic cell death; however, much remains to be explored about the molecules that are expressed in an NF-κB-dependent manner and which support monocyte-macrophage differentiation. Using the monocytic cell line THP-1, and peripheral blood monocytes, we show here a sustained increase in A20 expression during monocyte-macrophage differentiation, which coincided with high NF-κB-dependent transcriptional activity. Depletion of NF-κB by stable expression of a super-repressor form of IκBα in THP-1 cells caused remarkable cell death during phorbol 12-myristate 13-acetate (PMA)-induced differentiation. A20 expression in these cells did not alter this NF-κB suppression, but was sufficient to protect the cells and restore the cell surface expression of a differentiation marker (CD11b) and phagocytic activity. Mutational analyses revealed that this A20 activity requires the carboxy-terminal zinc-finger domain, but not its deubiquitinase activity. Based on these findings, we conclude that A20, when ectopically expressed, can support both survival and differentiation of THP-1 cells in the absence of sustained NF-κB activity.
DOI	10.1002/jcb.26308
PMID	28771803