PMID- 17329253
OWN - NLM
STAT- MEDLINE
DCOM- 20070614
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 17
DP  - 2007 Apr 27
TI  - XAF1 mediates tumor necrosis factor-alpha-induced apoptosis and X-linked 
      inhibitor of apoptosis cleavage by acting through the mitochondrial pathway.
PG  - 13059-72
AB  - Tumor necrosis factor-alpha (TNF-alpha) and Fas ligand induce apoptosis by 
      interacting with their corresponding membrane-bound death receptors and 
      activating caspases. Since both systems share several components of the 
      intracellular apoptotic cascade and are expressed by first trimester 
      trophoblasts, it is unknown how these cells remain resistant to Fas ligand while 
      sensitive to TNF-alpha. XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated 
      factor 1) is a proapoptotic protein that antagonizes the caspase-inhibitory 
      activity of XIAP. Here, we demonstrated that XAF1 functions as an alternative 
      pathway for TNF-alpha-induced apoptosis by translocating to the mitochondria and 
      promoting XIAP inactivation. In addition, we showed that the overexpression of 
      XAF1 sensitized first trimester trophoblast cells to Fas-mediated apoptosis. 
      Furthermore, we also determined that the differential expression of XAF1 in first 
      and third trimester trophoblast cells was due to changes in XAF1 gene 
      methylation. Our results establish a novel regulatory pathway controlling 
      trophoblast cell survival and provide a molecular mechanism to explain 
      trophoblast sensitivity to TNF-alpha and the increased number of apoptotic 
      trophoblast cells observed near term. Aberrant XAF1 expression and/or 
      localization may have consequences for normal pregnancy outcome.
FAU - Straszewski-Chavez, Shawn L
AU  - Straszewski-Chavez SL
AD  - Department of Molecular, Cellular and Developmental Biology, Yale University, New 
      Haven, Connecticut 06520, USA.
FAU - Visintin, Irene P
AU  - Visintin IP
FAU - Karassina, Natasha
AU  - Karassina N
FAU - Los, Georgyi
AU  - Los G
FAU - Liston, Peter
AU  - Liston P
FAU - Halaban, Ruth
AU  - Halaban R
FAU - Fadiel, Ahmed
AU  - Fadiel A
FAU - Mor, Gil
AU  - Mor G
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20070228
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XAF1 protein, human)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mitochondria/*metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Pregnancy
MH  - Pregnancy Trimester, First/metabolism
MH  - Pregnancy Trimester, Third/metabolism
MH  - Trophoblasts/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - X-Linked Inhibitor of Apoptosis Protein/*metabolism
MH  - fas Receptor/metabolism
EDAT- 2007/03/03 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/03/03 09:00
PHST- 2007/03/03 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/03/03 09:00 [entrez]
AID - S0021-9258(18)95079-9 [pii]
AID - 10.1074/jbc.M609038200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Apr 27;282(17):13059-72. doi: 10.1074/jbc.M609038200. Epub 2007 
      Feb 28.