Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist
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منابع مشابه
Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1.
ABT-737 is a small-molecule antagonist of BCL-2 currently under evaluation in clinical trials in the oral form of ABT-263. We anticipate that acquired resistance to this promising drug will inevitably arise. To study potential mechanisms of resistance to ABT-737, we derived resistant lines from initially sensitive OCI-Ly1 and SU-DHL-4 lymphoma cell lines via long-term exposure. Resistance was b...
متن کاملThe Modeling and Analysis of the Apoptotic BAD/tBID/BAK Pathway as a Chemical Reaction Network
Apoptosis, or programmed cell death, is an essential process in all multi-cellular organisms. It is indispensable to an organism’s survival, preventing the malicious propagation of DNA damage and pathogenic alterations, through the clean disposal of afflicted cells. The BAD/tBID/BAK pathway is a portion of the apoptosis molecular pathway, albeit an important pathway since it is known to be dere...
متن کاملtBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c.
TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates to mitochondria. Immunodepletion and gene disruption indicate BID is required for cytochrome c release. Surprisingly, the three-dimensional structure of this BH3 domain-only molecule revealed two hydrophobic alpha-helices suggesting tBID itself might be a pore-forming protein. Instead, we demonst...
متن کاملMcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation.
The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL but not Mcl-1, which may confer resistance to this novel agent. Here, we show that Mcl-1 down-regulation by the cyclin-dependent kinase (CDK) inhibitor roscovitine or Mcl-1-shRNA dramatically increases ABT-737 lethality in human leukemia cells. ABT-737 induces Bax conformational change but fails to activate Bak or trigger Bax translocation. Coad...
متن کاملMCL-1ES Induces MCL-1L-Dependent BAX- and BAK-Independent Mitochondrial Apoptosis
MCL-1 (myeloid cell leukemia-1), a member of the BCL-2 family, has three splicing variants, antiapoptotic MCL-1L, proapoptotic MCL-1S, and MCL-1ES. We previously reported cloning MCL-1ES and characterizing it as an apoptotic molecule. Here, we investigated the molecular mechanism by which MCL-1ES promotes cell death. MCL-1ES was distinct from other proapoptotic BCL-2 members that induce apoptos...
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ژورنال
عنوان ژورنال: Oncogene
سال: 2007
ISSN: 0950-9232,1476-5594
DOI: 10.1038/sj.onc.1210771