(ankyrine repeat,ank)

Transkript

1 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No. 4 2B,2 B ( (nuclear factor B,NF2 B),,,,,,,NF2 B NF2 B,, NF2 B ; ; I B ; X(2004) R :A 2B,100, main,rhd), DNA IB (nuclear location signal,nls) 3 NF2B C :2002 (Z02044) :361004, : [2 ] : P65 (RelA) RelB crel,c, ;P50 (NF2B1) P52 (NF2B2),,, ( P105 P100) [1 ] NF2B,C, (ankyrine repeat,ank) 2 NF2B AIDS,,NF2B IB,NF2B,, NF2B,,,IB N, NF2B,,, 26S, IB NF2 1 NF2B B IB,, NF2B Sen 1986 B B B, inos 52GGGRNNYYCC23 (R, Y,N [ 3] ),NF2BΠRel NF2B, TNF2 IL21, LPS, p65πp50,nf2 ( PKC) BΠRel 300 ( PHA) ( CONA) ( PMA) N, Rel ( Rel2homologe do2 NF2B 3. 1 NF2B : :NF2B,TNF2 IL21,TNF2 IL21, TNF2 IL21NF2B ;NF2B

2 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No IL26 IL28, :NF2B,,IB P105 A20, NF2B, NF2B,,NF2B,,,, NF2B B, NF2B,, NF2B IL21 TNF2 IL210 IL2l3,,IL210 IL2l3 NF2B, (cypgs) PGA PGJ IKK B, IKK,IKK 179 IKK [7 ], IB, IB,IKK NF2B COX2, COX2,IKK [4 ] 3. 2 IKK2IB IB 37 (Ank),33, RHD [5 ] IB 8 [6 ] : P100 P105 IB IB IB IB Bcl2 3 IB2R IB C PEST, NF2B DNA,N,,IB IB Ank NF2B, ReLΠNF2B RHD, NF2B NLS, IB IB,,NF2B MEKK1 NF2B, NF2B,NF2B IB, IB,NF2B B, NF2B2IB, Yamazaki [3 ] IB IBz,,LPS IL21 TIR (TLR IL21R ) NF2B [3 ],, N 6, NF2B IB (IB IB IB ),NF2B,P50 P65 NF2B, IBz P65ΠP50 P50ΠP50 DNA, IBz IL21 LPS TNF2 NF2B, IBz RNA LPS NF2B,, TNF2, IBz IB NF2 IB ( IKK) IKK IKK Ser32 Ser36 IB Serl9 Ser23 IB Ser18 Ser22 IB F 2TrCP, IB Lys21 Lys22,IB 26S,,NF2B,, [8 ] IKK IKK,NF2B (NF2B2 inducing kinase,nik) MEKK1 (mitogen2activated pro2 tein kinaseπextracellular signal2regulated kinase kinase 1) IKK, IKK IKK, TNF TNFR, TNFR (TRADD) (RIP) TNFR (TRAF22), NIKIL21 TNF NIK NIK IB IKK, IB, NF2B MEKK12Π2 [9 ] 3. 3 P65 NF2B,NF2B P65 C

3 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No. 4 TD RHD [10 ] TNF, HeLa, (casein kinase,ck ) NF2B Ser529,IL21 CK P65,P65 Ser536 IKK,PMA, P65 TD2, Ca 2 + Π,HDAC NF2B (Ca 2 + Πcalmodulin kinase,cam ) P65 C [11 ], RHD Ser276 PKAc MSK1 PKAc IB, IB P65 Ser276 ;MSK1 ERKP38, TNF Ser276 P65 PKC 2Π2, IL21 TNF, P65 N PKC A(PKA) P65 NF2B CBP[cAMP2 responsive element binding protein ( CREB) 2binding pro2 tein], NF2B, P65 NF2B,,P65,,, 2A (protein phosphatase 2A,PP2A) IL21 P65 [10 ] 3. 4 P65 P65,NF2 B CBP (homologue) p300 PCAF (p300πcbp2associated fac2 tor) P65 CBPΠP300 PCAF,Lys , ( histone deacetylase, HDAC), P65 DNA2B P65ΠP50 DNA2B P65 DNA2 B Lys ,NF2B DNA (minor groove) P50 CBPΠP300 PCAF IB NF2B, Chen [12 ] P65,, IB, NF2B HDAC1 HDAC2 P65 TNF P65 DNA2B, IBDNA2B, NF2B [13 ] NF2B HDAC3 P65 IB, NF2B, IB NF2B,IB NF2B DNA Mayo [14 ] HDAC NSCLS, IL28 Bcl2XL MMP29 NF2B, Akt ( PI3K ) NF2B P65 Chen Kiernan [12,15 ] P300 HDAC3 P65 NF2B,P65 Chen P65 NF2B IB, NF2B IB NF2B, Kiernan P65 DNA2B, IB P65 IB Kiernan Chen P65, HDAC TSA,,TSA, (bas2 al transcription machine) Chen TNF2 TSA P65 DNA,, P65 DNA2B, Kier2 nan P65 DNA2B,IB NF2B, P65 DNA,, P65 NF2B DNA2B, IB, P65,P300 PCAF P65 NF2B (turn2off) P65ΠP50 DNA2B, ,IB P65ΠP ,NF2B,P300 PCAF P65 Lys P65 DNA2B

4 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No ,HDAC1 HDAC2 HDAC3 P65,Kiernan HDAC2 HDAC3 P65, HDAC1,,P65 NF2B 3. 5 PI3K PI3K(phosphatidylinositol 32kinase) NF2B P65 (transaction),pi3k Akt NF2B [16 ] PI3K 293 HeLa ME180, TNF NF2B DNA,,Akt IKK IB [17 ] PI3K LPS PMA NF2B, TNF (ce2 ramide) H 2 O 2 Ocadaic NF2B [18 ] PI3K IKK,PI3K P65 :Hep G2,PI3KIL2 1 P65 IB NF2B DNA NIH3T3, Ras P65, PI3KΠAkt [19 ], Akt IKK P38 P65,Ser529 Ser536 [20 ],Mayo [14 ] PI3KΠAkt NF2B,HDAC NF2B, NSCLS Beraud Tyr ( Per2 NF2B, vanadate, Pv) IBTyr42 NF2 NF2B,IBSer B,,Tyr42 IB,, IB NF2B, PI3K, T Pv, PI3K P85a Src 2 (SH2) Tyr42 IB,PI3K Wortmannin,Pv NF2B, TNF IL21 NF2B, Wortmannin Pv Akt NF2B Beraud PI3K NF2B Tyr, PI3K NF2B,Vermeulen [5 ] PI3K Wortmannin LY L929sA PI3KTNF NF2B, P65Π P50 DNA, Gal4 TNF P65 3, Wortmannin LY294002, MAPKH89 ( PKA MSK ), PI3K TNF NF2B DNA, TNF P65, PI3K NF2B P65,,,Vermeulen 4 NF2B,NF2B [1 ], NF2B DNA2B NF2B :NF2B,, [3 ],NF2B NF2B, NF2B NF2B 1 Hiscott J, Kwon H, Genin P. Hostile takeovers : viral appropriation of the NF2 B pathway[j ].J Clin Invest,2001,107 (2) : Perkins ND. The RelΠNF2 B family : friend and foe [J ]. Trends Biochem Sci,2000,25 (9) : Yamazaki S,Muta T,Takeshige K. A novel I B protein, I B2zeta,induced by proinflammatory stimuli, negatively regulates nuclear factor2 B in the

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