?????TNF????

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?????TNF????

• ???????????????
• ?00??12?17?

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• Death Receptors Signaling and Modulation
• Science 1998 2811305-
• Avi Ashkenazi, Vishva M. Dixit
• The authors are in the Department of Molecular
  Oncology, Genentech Inc., 1 DNA Way, South San
  Francisco, CA 94080, USA. E-mail aa_at_gene.com,
  dixit_at_gene.com

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????

• ???????????????????????????,???????????
  ????
• ??????,?????????????? (Fig.1)

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??????

• ??????TNF??????????????,??????????????
  ???????????(DD)?????? (Fig.2)

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??????(Fig.2)

• 1?????????CD95(Fas/Apol)
• 
  TNFR1(p55/CD120a)
• 2???????DR3(Apo3/WSL- 1
• 
  /TRAMP/LARD)
• DR4
• 
  DR5(Apo2/TRAIL-R2
• 
  /TRICK2/KILLER)
• 3? ?? CD95L------CD95
• TNF-a ------TNFR1
  
• Apo3L------DR3
• Apo2L------DR4,DR5

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?? TNF????

• 1?TNF?TNF??
• TNF(tumor necrosis factor)????????,???????
  ????????????????????????T???????
• TNF????????TNFR1?TNFR2??????????
  TNFR1???????,?TNFR2??????????

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?? TNF????

• 2? TNF???????
• ??????????????????
• 3? TNF???? (Fig.3)
• 1)TNF-a?TNFR1?????,?TNFR1??????(??TNF-a
  ???TNFR1????)
• 2)???TNFR1??????????????(DD)??????????(
  TRADD?FADD?TRAF2?RIP)?
• 3)?????????????,?????caspase
  8????????caspases,????????,??????????
• 4)TNF??????????RIP,TRAF2?,????NIK?MEKK,
  ????NF-KB?c-Jun,???????

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????????

• 1?CD95??
• ????
• 1)???????,?????T???
• 2)T???NK????????????????
• 3)????????(??)??????
• ??(Fig.4)(Fig.5)
• 1)CD95L????????,??CD95L???????
  Fas??,???????,?Fas????????
• 2)FADD?Fas??????
• 3)FADD??DED?????caspase
  8?DED??,??caspase 8,???caspase???????,?????????

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????????

• 2?DR3?? (Fig.3)
• ??DR3?????TNFR1???????
• 1)??TRADD,TRAF2?RIP??????NF-KB,?
  ????
• 2)??TRADD,FADD?caspase
  8?,???????
• DR3???TNFR1??????????????????????

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????????

• 3?DR4?DR5??
• ??Apo2L?DR4?DR5???,???????????????????
  ?
• ???? (Fig.6) DR4?DR5??????????caspase,
  ????FADD????
• DcRs?DR4?DR5????? DcRs?DR4?DR5????,??A
  po2L,????Apo2L????????
• DcRs??DcR1?DcR2???

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?????

• ???,?????TNF???????????,??????????????????
  ?????????????????????????,??????????????????????

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