The prosurvival Bcl-2-family member Bfl-1/A1 is a transcriptional target of nuclear factor-κB (NF-κB) that is overexpressed in many human tumors and is a means by which NF-κB inhibits apoptosis, but its mode of action is controversial. To better understand how Bfl-1 functions, we investigated its interaction with proapoptotic multidomain proteins Bax and Bak, and the BH3-only proteins Bid and tBid. We demonstrate that in living cells Bfl-1 selectively interacts with Bak and tBid, but not with Bax or Bid. Bfl-1/Bak interaction is functional as Bfl-1 suppressed staurosporine (STS)-induced apoptosis in wild-type and Bax-deficient cells, but not in Bak-/- cells. We also show that Bfl-1 blocks tumor necrosis factor-α (TNFα)-induced activation of Bax indirectly, via association with tBid. C-terminal deletion decreased Bfl-1's interaction with Bak and tBid and reduced its ability to suppress Bak- and tBid-mediated cell death. These data indicate that Bfl-1 utilizes different mechanisms to suppress apoptosis depending on the stimulus. Bfl-1 associates with tBid to prevent activation of proapoptotic Bax and Bak, and it also interacts directly with Bak to antagonize Bak-mediated cell death, similar to Mcl-1. Thus, part of the protective function of NF-κB is to induce Mcl-1-like activity by upregulating Bfl-1.

Original languageEnglish (US)
Pages (from-to)1421-1428
Number of pages8
Issue number10
StatePublished - Feb 28 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


  • A1
  • Apoptosis
  • Bak
  • Bcl2a1
  • Bfl-1
  • tBid


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