A20 restores phorbol ester-induced differentiation of THP-1 cells in the absence of nuclear factor-B activation

作者：Osako Miho; Itsumi Momoe^*; Yamaguchi Haruka; Takeuchi Hiroaki; Yamaoka Shoji^*

来源：Journal of Cellular Biochemistry, 2018, 119(2): 1475-1487.

DOI：10.1002/jcb.26308

• A20
• cell differentiation
• cell survival
• monocyte
• macrophage
• NF-B

A20, also referred to as tumor necrosis factor alpha (TNF)-induced protein 3 (TNFAIP3), is an ubiquitin-editing enzyme whose expression is enhanced by NF-B activation, and plays an important role in silencing NF-B activity. Another well-known role for A20 is to protect cells from TNF-induced apoptosis. Depletion of NF-B 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-B-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-B-dependent transcriptional activity. Depletion of NF-B by stable expression of a super-repressor form of IB 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-B 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-B activity.

• 出版日期2018-2