ライフサイエンスコーパス: IRF-2

1 on domain of Interferon Regulatory Factor-2 (IRF-2).

2 ) family of transcription factors, IRF-1 and IRF-2.

3 ssociated with greatly reduced expression of IRF-2.

4 F-1 mRNA and protein but unchanged levels of IRF-2.

5 sion, with a rapid and transient decrease of IRF-2.

6 r-1 (IRF-1) and the constitutively expressed IRF-2.

7 hese markers lie some distance (500 kb) from IRF-2.

8 , suggesting a novel anti-apoptotic role for IRF-2.

9 n anticooperative interaction with IRF-1 and IRF-2.

10 he amount of inducible CIITA mRNA depends on IRF-2.

11 re potent activators of the H4 promoter than IRF-2.

12 specific FasL promoter binding by IRF-1 and IRF-2.

13 We identify interferon regulatory factor-2 (IRF-2), a member of the interferon regulatory factor fam

14 onal activator IRF-1 and the closely related IRF-2, a repressor of interferon-induced gene expression

15 nd 3 and IFN regulatory factor-1 (IRF-1) and IRF-2 activation failed to reveal differences between th

16 1 acts as a transcriptional activator, while IRF-2 acts as a repressor.

17 vely, these data support the hypothesis that IRF-2 acts as a transcriptional repressor of Casp1, and

18 Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signali

19 tion studies showed that Blimp-1, IRF-1, and IRF-2 all bind the IFN-beta promoter in vivo, as predict

20 We conclude that IRF-2 and BID activate gp91(phox) promoter activity in t

21 Constitutively expressed IRF-2 and IFN-gamma-induced IRF-1 factors specifically b

22 ve identified two members of the IRF family (IRF-2 and IRF-3) that specifically bind to these sites.

23 ISRE in the 32kb-150 reporter gene recruits IRF-2 and mediates TPA-induced activation of a reporter

24 Both bind endogenous IRF-1 and IRF-2 and regulate transcription in an IRF-1/2-dependent

25 Although IRF-2 and VCAM-1 expression diminishes on adult muscle f

26 is, responses of peritoneal macrophages from IRF-2(+/+) and IRF-2(-/-) mice to apoptotic stimuli, inc

27 profiling of liver RNA samples derived from IRF-2(+/+) and IRF-2(-/-) mice treated with saline or LP

28 Liver sections from IRF-2(+/+) and IRF-2(-/-) mice were analyzed 6 h after a

29 from IRF-2-/- M phi to approximately 50% of IRF-2+/- and C57BL/6 levels.

30 Unexpectedly, IRF-2-/-, IRF-2+/- and C57BL/6 M phi produced comparable levels of

31 IFN regulatory factors (IRFs) such as IRF-1, IRF-2, and IFN consensus sequence binding protein (ICSBP

32 while all other IRF proteins tested (IRF-1, IRF-2, and ISGF3-gamma) were detected in these cells.

33 lustrates the crucial roles for AP-1, IRF-1, IRF-2, and STAT1 in the regulation of murine TLR9 expres

34 the ability of M phi from INF-2 homozygous (IRF-2-/-) and heterozygous (IRF-2+/-) knockout mice to p

35 Type IV promoter IRF-E is also activated by IRF-2, another member of the IRF family that generally a

36 In addition to IRF-1, IRF-2, another member of the IRF family, also activates

37 imens were stained with polyclonal IRF-1 and IRF-2 antibodies using an avidin-biotin-peroxidase compl

38 IRF-2 antisense oligonucleotide pretreatment did not aff

39 These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulati

40 that in the developing mouse lens, IRF-1 and IRF-2 are expressed at high levels in differentiated len

41 gamma-stimulated PGE(2) release, identifying IRF-2 as negative regulator of this promoter.

42 Here we show that IRF-1 and IRF-2 bind to both cellular TFIIB, a component of the ba

43 These proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2, t

44 fector arm of the interferon gamma response; IRF-2 binds to the same DNA consensus sequence and oppos

45 NA binding domain of one such family member, IRF-2, bound to DNA.

46 wed expression of IRF-1 and no expression of IRF-2 by immunohistochemistry.

47 IRF-1 and IRF-2 can co-occupy the IRF-E of the human CIITA type IV

48 Our results also indicate that IRF-1 and IRF-2 can cooperatively activate and co-occupy the IRF-E

49 obility shift assays revealed that IRF-1 and IRF-2 can simultaneously occupy the IRF-E of the CIITA T

50 ption factor interferon regulatory factor 2 (IRF-2) can activate histone H4 gene expression.

51 Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence

52 this endogenous mouse histone H4 gene in the IRF-2(-/-) cells.

53 e additional synergy observed with IRF-1 and IRF-2 coexpression is mediated by a region of DNA distin

54 S-inducible activation of the UBP43 gene and IRF-2 confers a basal transcriptional activity to the UB

55 IRF-2 constitutively binds to the two ISRE/IRF-E sites a

56 The truncated IRF-2 contained the DNA binding domain (DBD) and bound t

57 Together, these results indicate that IRF-2 contributes to transcriptional activation of the N

58 ivates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in

59 h alterations in growth characteristics, the IRF-2 DBD transfectants constitutively expressed higher

60 Phenotypically, the IRF-2 DBD transfectants exhibited reduced cell growth, a

61 nding the previously described phenotypes of IRF-2 defective mice are discussed.

62 fection of PCAF strongly enhanced IRF-1- and IRF-2-dependent promoter activities.

63 nuclear proteins, and have the properties of IRF-2-dependent transcriptional co-repressors that can i

64 These results indicate that IRF-1 and IRF-2 differ in their mechanism of NO. regulation and th

65 n of IFN regulatory factor-1 (IRF-1) but not IRF-2, double-stranded RNA-activated protein kinase, and

66 Furthermore, coexpression of IRF-1 and IRF-2 dramatically increased the capacity of both PU.1/I

67 2) maps to this region, and, as mice lacking IRF-2 exhibit a dermatologic phenotype resembling many a

68 into macrophages, both NMHC-A expression and IRF-2 expression were found to be up-regulated with a si

69 tumor suppressor loss and the development of IRF-2 expression with oncogenic activation.

70 Remarkably, deletion of the IRF-2 gene increases IFN-beta expression by expanding th

71 binding protein (ICSBP) genes were induced; IRF-2 gene transcription was not upregulated.

72 synchronized embryonic fibroblasts in which IRF-2 has been ablated.

73 analyses indicated that forced expression of IRF-2 has limited effects on cell cycle progression befo

74 constants, we show that Blimp-1, IRF-1, and IRF-2 have similar binding affinities for functionally i

75 Here, we show that IRF-1, IRF-2, ICSBP, and LSIRF/Pip are constitutively expressed

76 gainst IFN-responsive factors such as IRF-1, IRF-2, IFN consensus sequence binding protein, Stat1, an

77 Overexpression of IRF-2 in a type I latency cell line did not activate the

78 s observation, and to understand the role of IRF-2 in apoptosis, responses of peritoneal macrophages

79 To investigate the role of IRF-2 in control of cell proliferation, we have construc

80 y, these findings reveal a critical role for IRF-2 in endotoxicity, and point to a previously unappre

81 IRF-1 expression and the oncogenic effect of IRF-2 in human and murine tumor models, including human

82 Overexpression of IRF-1 or IRF-2 in K562 cells leads to transactivation of gp91(pho

83 Conversely, the absence of IRF-2 in macrophages resulted in a significant increase

84 point to a previously unappreciated role for IRF-2 in the regulation of apoptosis.

85 jection of LPS to evaluate the importance of IRF-2 in the regulation of endotoxicity.

86 dent activation of Qp is largely mediated by IRF-2 in these cells.

87 As a consequence, IRF-2 incorporation into enhanceosomes restricts the num

88 Hence, IRF-2 induces a cell death response involving the Fas/Fa

89 cted antisense oligonucleotides for IRF-1 or IRF-2 into R3T3 cells and observed that IRF-1 antisense

90 Mice with a targeted mutation in IRF-2 (IRF-2(-/-)) were studied after injection of LPS t

91 Our results indicate that IRF-1, IRF-2, IRF-3, and IRF-7 can all regulate histone H4 gene

92 the transcriptional contributions of IRF-1, IRF-2, IRF-3, and IRF-7 using transient transfection ass

93 Unexpectedly, IRF-2-/-, IRF-2+/- and C57BL/6 M phi produced comparable

94 These data strongly suggest that IRF-2 is a negative regulator of Qp and may contribute t

95 IRF-2 is a negative regulator of the interferon response

96 IFN-stimulated gene factor-3 gamma, although IRF-2 is additionally detected as binding to the middle

97 Expression of IRF-1 and IRF-2 is altered in human breast cancer compared with no

98 Our results suggest that IRF-2 is an active player in E2F-independent cell cycle-

99 binding domain and the C-terminal region of IRF-2 is crucial for transcriptional repression.

100 FDC-P1 cell line (F2) in which expression of IRF-2 is doxycycline (DOX)-inducible, and a control cell

101 Also, IRF-2 is identified by electrophoretic mobility shift as

102 Since expression of IRF-1 and IRF-2 is increased in response to interferons, the Qp ac

103 ssor motif located near the COOH-terminal of IRF-2 is not active in muscle cells, but instead an acid

104 IRF-2 is not dependent upon cytokines for expression or

105 f histone H4 transcription are restored when IRF-2 is reintroduced to these cells.

106 In this work, expression of IRF-2 is shown to be inversely associated with Qp status

107 However, the levels of IRF-2, JAK2, and STAT 91 were similar in both ME180 and

108 reduction of IFN-gamma induced CIITA mRNA in IRF-2 knock-out mice was due to the reduction of the typ

109 pression, we assayed for CIITA expression in IRF-2 knock-out mice.

110 mma induced CIITA expression were reduced in IRF-2 knock-out mice.

111 ved from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utili

112 IRF-2 knockout mice also failed to sustain LPS-inducible

113 NF-2 homozygous (IRF-2-/-) and heterozygous (IRF-2+/-) knockout mice to produce NO. following LPS and

114 stably transfected with a truncated form of IRF-2 lacking the transcriptional repressor domain.

115 Forced expression of either IRF-1 or IRF-2 leads to FasL promoter activation in T cells and F

116 e inversely associated with Qp status, i.e., IRF-2 levels are high in type III latency (when Qp is in

117 nued cell growth in the presence of elevated IRF-2 levels results in polyploidy (>4n) or genomic disi

118 These data indicate that IRF-2, like IRF-1, plays a critical role in the regulati

119 IRF-2-/- M phi produced less LPS-induced NO2- than IRF-2

120 synergized to increase NO2- production from IRF-2-/- M phi to approximately 50% of IRF-2+/- and C57B

121 Compared with IRF-2(+/+) macrophages, STAT3alpha mRNA was up-regulated

122 IRF-2(-/-) macrophages exhibited a consistently higher i

123 IRF-2(-/-) macrophages exhibited increased basal and gli

124 Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LP

125 nstitutively or after gliotoxin treatment of IRF-2(-/-) macrophages, whereas STAT3beta mRNA was down-

126 nificantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairmen

127 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages.

128 nd protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages.

129 s markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages.

130 IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages.

131 e-1 abolished gliotoxin-induced apoptosis in IRF-2(-/-) macrophages.

132 In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced I

133 ene encoding interferon regulatory factor-2 (IRF-2) maps to this region, and, as mice lacking IRF-2 e

134 Overexpression of IRF-1, but not IRF-2, markedly augments cathepsin S promoter activity i

135 sensus sequence as IRF-1, we postulated that IRF-2 may also regulate NO..

136 Thus, IRF-2 may have a dual function in histone H4 gene transc

137 d alterations in the expression of IRF-1 and IRF-2 may occur in breast cancer tissue compared with no

138 This element interacts with IRF-1 and IRF-2, members of the interferon regulatory factor famil

139 tly lower than levels seen in LPS-challenged IRF-2(+/+) mice.

140 IRF-2(-/-) mice exhibited greater numbers of apoptotic K

141 f peritoneal macrophages from IRF-2(+/+) and IRF-2(-/-) mice to apoptotic stimuli, including the fung

142 iver RNA samples derived from IRF-2(+/+) and IRF-2(-/-) mice treated with saline or LPS, we identifie

143 IRF-2(-/-) mice were also more refractory to TNF-alpha c

144 Liver sections from IRF-2(+/+) and IRF-2(-/-) mice were analyzed 6 h after a typically leth

145 IRF-2(-/-) mice were highly refractory to LPS-induced le

146 L-12R beta 2 mRNA levels from LPS-challenged IRF-2(-/-) mice were significantly different after 1, 6,

147 es that were significantly down-regulated in IRF-2(-/-) mice, including Stat3, which has been reporte

148 ere significantly elevated in LPS-challenged IRF-2(-/-) mice, levels of IL-1, IL-12, and IFN-gamma mR

149 e were dead within 2 wk postinfection, while IRF-2-/- mice contained less splenic Brucella CFU than w

150 box and an ISRE motif with an internal IRF-1/IRF-2 motif.

151 sses a mutated IRF-2, representing the first IRF-2 mutation identified in a human tumor cell line.

152 To understand the effect of loss of IRF-2 on the endogenous CIITA expression, we assayed for

153 Our data suggest that the IRF-2 oncoprotein regulates a critical cell cycle checkp

154 We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene

155 The IFN regulatory factor-2 (IRF-2) oncoprotein controls the cell cycle-dependent exp

156 /- M phi produced less LPS-induced NO2- than IRF-2+/- or C57BL/6 M phi.

157 scription factor and show that expression of IRF-2 parallels that of VCAM-1 during mouse skeletal myo

158 IRF-2 predominates in macrophages that express the gp91(

159 Finally, we found no abnormalities of IRF-2 protein expression or distribution in skin biopsie

160 re much more likely to express the oncogenic IRF-2 protein than was normal tissue.

161 Since IRF-2 recognizes the same consensus sequence as IRF-1, w

162 n of different IRF combinations reveals that IRF-2 reduces IRF-1 or IRF-3 dependent activation, but d

163 n their mechanism of NO. regulation and that IRF-2 regulates inducible NO. synthase post-transcriptio

164 repressor of Casp1, and that the absence of IRF-2 renders macrophages more sensitive to apoptotic st

165 tic tumor cell line that expresses a mutated IRF-2, representing the first IRF-2 mutation identified

166 resembling many aspects of human psoriasis, IRF-2 represents an attractive positional candidate.

167 In transient transfection assays, IRF-2 represses the activity of Qp-reporter constructs.

168 178) in the central portion of the protein (IRF-2[S]) cannot bind to these co-repressors and cannot

169 We set out to establish whether variation in IRF-2 sequence or expression was related to the developm

170 The carboxyl-terminal basic region of IRF-2 serves as an activation domain in this context.

171 Interferon regulatory factor 2 (IRF-2) sites were altered by significantly associated SN

172 of Burkitt lymphoma cells was attributed to IRF-2, suggesting that interferon-independent activation

173 ng the same C- terminal repression domain as IRF-2, suggesting that the relative conformation of the

174 In addition, we found that IRF-1 and IRF-2 synergistically activate the CIITA Type IV promote

175 ein levels were also significantly higher in IRF-2(-/-) than control macrophages.

176 An alternatively spliced form of IRF-2 that lacks two amino acids (valines 177 and 178) i

177 cription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment o

178 TPA treatment leads to recruitment of IRF-2 to 32kb-150 of the endogenous NMHC-A gene and acet

179 oth IRF-1 and its transcriptional antagonist IRF-2 to activate Qp, EBV has evolved not only a mechani

180 These results imply active repression by IRF-2 to keep p21WAF1/Cip1 transcriptionally silent.

181 Virus infection induces recruitment of IRF-2 to some of the endogenous IFN-beta enhancers as pa

182 documenting binding of GATA-4 and IRF-1 and IRF-2 to the first intron sequence.

183 the G1 phase by isoleucine deprivation, and IRF-2 was induced by DOX on release of cells from the ce

184 IRF-2 was previously considered a passive antagonist to

185 coding, and adjacent untranslated regions of IRF-2 were screened in individuals from 4q-linked famili

186 Mice with a targeted mutation in IRF-2 (IRF-2(-/-)) were studied after injection of LPS to evalu

187 IRF-2, which is known to either repress or activate targ