(ankyrine repeat,ank)

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234 2004 27 4 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 ; 1001-103X(2004) - 04-0234 - 04 R392. 11 :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

2004 27 4 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No. 4 235 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

236 2004 27 4 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,Lys122 123, ( histone deacetylase, HDAC), P65 DNA2B P65ΠP50 DNA2B P65 DNA2 B Lys122 123,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, 10-10 10-13,IB P65ΠP50 10-9,NF2B,P300 PCAF P65 Lys122 123 P65 DNA2B

2004 27 4 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No. 4 237,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 LY294002 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) :1432151. 2 Perkins ND. The RelΠNF2 B family : friend and foe [J ]. Trends Biochem Sci,2000,25 (9) :4342440. 3 Yamazaki S,Muta T,Takeshige K. A novel I B protein, I B2zeta,induced by proinflammatory stimuli, negatively regulates nuclear factor2 B in the

238 2004 27 4 Foreign Medical Sciences Section of Immunology,July 2004,Vol. 27,No. 4 nuclei[j ].J Biol Chem,2001,276 (29) :27657227662. 4 Rossi A,Kapahi P,Natoli G,et al. Anti2inflammatory cyclopentenone pros2 taglandins are direct inhibitors of I B kinase [ J ]. Nature, 2000, 403 (6765) :1032108. 5 Vermeulen L,De Wilde G,Notebaert S,et al. Regulation of the transcrip2 tional activity of the nuclear factor2 B p65 subunit [J ]. Biochem Pharma2 col,2002,64 (526) :9632970. 6 Israel A. The IKKcomplex : an integrator of all signals that activate NF2 B [J ]? Trends Cell Biol,2000,10 (4) :1292133. 7 Verma UN,Yamamoto Y,Prajapati S,et al. Nuclear role of Ikgamma B ki2 nase2gammaπnf2kappab essential modulator ( IKK gammaπnemo) in NF2 kappa B2dependent gene expression[j ].J Biol Chem,2004,279 (5) :35092 3515. 8 Wang X,Adhiakri N,Li Q,et al. The Role of {beta}2transducin Repeat2 Containing Protein ( beta 2TrCP) in the Regulation of NF2 kappa B in Vascular Smooth Muscle Cells[J ]. Arterioscler Thromb Vasc Biol,2004,24 (1) :85290. 9 Nawata R,Yujiri T,Nakamura Y,et al. MEK kinase 1 mediates the anti2 apoptotic effect of the Bcr2Abl oncogene through NF2 B activation[j ]. On2 cogene,2003,22 (49) :777427780. 10 Schmitz ML,Bacher S,Kracht M. I B2independent control of NF2 B ac2 tivity by modulatory phosphorylations[j ]. Trends Biochem Sci,2001,26 (3) :1862190. 11 Jang MK, Goo YH,Sohn YC,et al. Ca 2 + Πcalmodulin2dependent protein kinase stimulates nuclear factor2kappa B transactivation via phosphory2 lation of the p65 subunit[j ].J Biol Chem,2001,276 (23) :20005220010. 12 Chen Lf,Fisce W,Verdin E,et al. Duration of nuclear NF2 B action reg2 ulated by reversible acetylation [J ]. Science, 2001, 293 (5535) : 16532 1657. 13 Ashburner BP,Westerheide SD,Baldwin AS Jr. The p65 ( RelA) subunit of NF2 B interacts with the histone deacetylase ( HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression[j ]. Mol Cell Biol,2001,21 (20) :706527077. 14 Mayo MW,Denlinger CE,Broad RM,et al. Ineffectiveness of HDAC in2 hibitors to induce apoptosis involves the transcriptional activation of NF2 B through the Akt pathway [J ]. J Biol Chem,2003,278 (21) : 189802 18989. 15 Kiernan R,Bres V,Ng RW,et al. Post2activation turn2off of NF2kappa B2 dependent transcription is regulated by acetylation of p65 [ J ]. J Biol Chem,2003,278 (4) :275822766. 16 Kobayashi N,Mita S,Yoshida K,et al. Celiprolol activates enos through the PI3K2Akt pathway and inhibits VCAM21 Via NF2 B induced by oxi2 dative stress[j ]. Hypertension,2003,42 (5) :100421013. 17 Manna SK,Aggarwal BB. Wortmannin inhibits activation of nuclear tran2 scription factors NF2 B and activated protein21 induced by lipopolysac2 charide and phorbol ester[j ]. FEBS Lett,2000,473 (1) :1132118. 18 Manna SK,Aggarwal BB. Wortmannin inhibits activation of nuclear tran2 scription factors NF2 B and activated protein21 induced by lipopolysac2 charide and phorbol ester[j ]. FEBS Lett,2000,473 (1) :1132118. 19 Madrid LV,Wang CY, Guttridge DC,et al. Akt suppresses apoptosis by stimulating the transactivation potential of the RelAΠp65 subunit of NF2 B [J ]. Mol Cell Biol,2000,20 (5) :162621638. 20 Madrid LV,Mayo MW,Reuther J Y,et al. Akt stimulates the transactiva2 tion potential of the RelAΠp65 Subunit of NF2 B through utilization of the I B kinase and activation of the mitogen2activated protein kinase p38[j ]. J Biol Chem,2001,276 (22) :18934218940. ( :2003-05 - 02), ( ),( ) HIV21,, ; ; 1001-103X(2004) 04-0238 - 03 R392. 11 :A 1988 Morgan : (182D501d) :100071, () [1 ], (), ( )