ライフサイエンスコーパス: AIP1

1 the Drosophila actin interacting protein 1 (AIP1).

2 in (Ras-GAP) as an ASK1-interacting protein (AIP1).

3 particularly toward its pro-apoptotic target AIP1.

4 insight into the function of ADF/cofilin and AIP1.

5 that cooperate with cofilin are Srv2/CAP and Aip1.

6 teracted with the proline-rich C terminus of AIP1.

7 timal expansion to determine the function of AIP1.

8 eing necessary for its interaction with ALIX/AIP1.

9 nds to ASK1, PP2A binds to the GAP domain of AIP1.

10 was markedly diminished by overexpression of AIP1.

11 NA encoding for ALG-2 interacting protein 1 (AIP1), a novel protein that interacts with ALG-2.

12 ASK1-interacting protein-1 (AIP1), a recently identified member of the Ras GTPase-ac

13 ion involved in L domain function that binds AIP1, a homolog of the yeast class E Vps protein Bro1.

14 nds on a direct interaction of Nef with Alix/AIP1, a protein associated with the endosomal sorting co

15 Aip1 (actin interacting protein 1) is ubiquitous in euka

16 In vitro, AIP1 actively disassembles filaments, caps barbed ends,

17 es, we undertook an extensive mutagenesis of AIP1 aimed at disrupting and mapping Aip1p interactions.

18 nd (iv) overexpression or siRNA silencing of AIP1/Alix and AP-2 revealed additive suppression of YPDL

19 velope protein colocalizes with MVB proteins AIP1/ALIX and VPS4B.

20 in proteins such as yeast Bro1 and mammalian AIP1/Alix are well-established participants in endosome

21 m20p, a member of the broadly conserved PalA/AIP1/Alix family, is required for Rim101p cleavage.

22 the EIAV YPDL motif; (ii) overexpression of AIP1/Alix or AP-2 mu2 subunit specifically inhibited YPD

23 omplex and with ALG-2-interacting protein 1 (AIP1/Alix) protein factors involved in early and late en

24 ng protein 1 or ALG-2-interacting protein X (AIP1/Alix).

25 known CIN85 interactors, c-Cbl, BLNK, Cbl-b, AIP1/Alix, SB1, and CD2 proteins, as well as the predict

26 t (i) an approximately 300-residue region of AIP1/Alix-(409-715) was sufficient for binding to the EI

27 vacuolar protein sorting factors, Tsg101 and AIP1/ALIX.

28 ates a 14-3-3-binding site but also opens up AIP1, allowing binding to TRAF2 and ASK1.

29 AIP1 alone has negligible effects on actin filament dyna

30 e rapid severing of cofilin-actin filaments, Aip1 also augments the monomer dissociation rate at both

31 AIP1 also binds the HIV-1 p6(Gag) and EIAV p9(Gag) prote

32 AIP1 also binds to the L domain in EIAV p9, and this bin

33 AIP1 also caps the barbed end of ADF/cofilin-bound actin

34 have shown that ASK1-interacting protein 1 (AIP1, also known as DAB2IP), a novel member of the Ras-G

35 e have shown that ASK-interacting protein 1 (AIP1, also known as DAB2IP), a novel member of the Ras-G

36 onally-restricted presentation of a modified AIP1 amino acid sequence (AIP1S).

37 1 binds to ALG-2 interacting protein X (Alix/AIP1), an interactor of apoptosis-linked gene protein 2

38 Here, we demonstrate that ALIX/AIP1, an ESCRT-associated host protein, is required for

39 TRAF2 and RIP1, known to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604

40 regulation of actin cable turnover, in which Aip1 and cofilin function together to "prune" tropomyosi

41 Our findings indicate a cooperative role of Aip1 and cofilin in pH-dependent cell migration, and the

42 Further, we reveal an unanticipated role for Aip1 and cofilin in promoting rapid turnover of yeast ac

43 By biochemical fractionation, we identify Aip1 and coronin as two proteins present in thymus extra

44 We purified both fission yeast and human Aip1 and investigated their biochemical activities with

45 g protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Se

46 By contrast, DN AIP1 and VPS4 had no effect on the efficiency of release

47 rnover proteins: actin interacting protein1 (AIP1) and actin depolymerizing factor (ADF).

48 a homologue of actin-interacting protein 1 (AIP1) and functions as a novel regulator of actin organi

49 ein), filament depolymerization (cofilin and Aip1), and actin monomer binding (profilin and cyclase-a

50 Coronin-1B and actin-interacting protein 1 (AIP1), and these differences were observed on both prefo

51 s that are involved, in concert with Arp2/3, Aip1, and ADF/cofilin, in rearrangements of the actin cy

52 ly, ADF can partially compensate for loss of AIP1, and AIP1 requires ADF for function.

53 ons of activities mediated by cofilin, Srv2, Aip1, and capping protein are required in vivo.

54 t protein 1 (Wdr1), the mammalian homolog of Aip1, and report that reductions in Wdr1 function produc

55 Previously we have shown that AIP1 (apoptosis signal-regulating kinase [ASK]1-interact

56 and the ASK1 binding and the GAP activity of AIP1 are critical for AIP1-enhanced ASK1 activation.

57 or depolymerization and that ADF/cofilin and AIP1 are distinct from gelsolin in modulating filament e

58 s that the combined activities of N-Srv2 and Aip1 are essential in vivo.

59 Fission yeast lacking Aip1 are viable and assemble cytokinetic contractile rin

60 ALG-2 and its putative target molecule, Alix/AIP1, are localized primarily in the cytoplasm of melano

61 These observations identify AIP1 as a component of the viral budding machinery, whic

62 We identified Aip1 as a critical factor responsible for the severing a

63 lament assembly pathway in vivo and identify Aip1 as a crucial factor for shifting the distribution o

64 hybrid system using the N-terminal domain of AIP1 as bait and identified homeodomain-interacting prot

65 is necessary for ALG-2 interaction with Alix/AIP1 as demonstrated using surface plasmon resonance spe

66 ecently identified ASK1-interacting protein (AIP1) as novel signal transducer in TNFalpha-induced ASK

67 -terminal deletion mutant of ALG-2 with Alix/AIP1, as might be expected from a model derived from the

68 -604 is essential for TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of AS

69 3-3 associates with an open, active state of AIP1 assessed by an in vitro pulldown assay.

70 n-interacting protein kinase 1 (HIPK1) as an AIP1-associated protein.

71 n of proapoptotic targets including PIDD and AIP1 at least to the same extent as wild-type p53.

72 Mutation of AIP1 at Ser-604 (AIP1-S604A) blocks TNF-induced complex

73 F treatment of EC induces phosphorylation of AIP1 at Ser-604 as detected by a phospho-specific antibo

74 th AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for TNF-induced ASK1 dephos

75 Both types of Aip1 bind actin filaments with micromolar affinities and

76 ar envelope glycoprotein and a high-affinity AIP1 binding site (YPD/SL) in their p6 Gag protein, as w

77 ling, and we found that although full-length Aip1 binds cofilin and F-actin, the C-terminal fragment

78 In contrast to 14-3-3, AIP1 binds preferentially to dephosphorylated ASK1.

79 AIP1 binds to the C-terminal domain of ASK1 via a lysine

80 PERIOD-like domain (amino acids 591-719) of AIP1 binds to the intact RING finger of TRAF2, and speci

81 Furthermore, RIP1 synergizes with AIP1 (but not AIP1-S604A) in inducing both JNK/p38 activ

82 nown to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for

83 ilin, suggesting that the strong activity of AIP1 cannot be explained by simple barbed end capping.

84 One is formation of an Aip1-cofilin cap at filament barbed ends.

85 ALG-2 and AIP1 colocalize in the cytosol and the presence of calci

86 er, our data support a critical role of PP2A-AIP1 complex in TNF-induced activation of ASK1-JNK apopt

87 tions, the physiologic processes the cofilin/Aip1 complex regulates, particularly in higher organisms

88 Thus, the N-terminus of AIP1 containing the C2 and GAP domains constitutively bi

89 ors withdrawal; thus, our data indicate that AIP1 cooperates with ALG-2 in executing the calcium-depe

90 Finally, PP2A and AIP1 cooperatively induce activation of ASK1-JNK signali

91 We created AIP1-deficient mice (AIP1-KO) from which mouse embryonic

92 To study this, we generated AIP1-deficient mice (KO mice).

93 male)-dependent aorta transplantation model, AIP1 deletion in the graft augmented neointima formation

94 IP1 mutant with a deletion of the PH domain (AIP1-DeltaPH), restores ER stress-induced IRE1-JNK/XBP-1

95 However, the mechanism by which AIP1 disassembles ADF/cofilin-bound filaments is not cle

96 Here, we show that AIP1 disrupts formation of the TLR4- TIRAP-MyD88 complex

97 Our results also demonstrate that Aip1 does not cap the barbed ends of actin filaments, as

98 Aip1 does not cap the barbed ends of filaments severed b

99 ndocytic sites, one depending on acp2(+) and aip1(+) during interphase and the other independent of a

100 e other independent of acp1(+), acp2(+), and aip1(+) during mitosis.

101 This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators.

102 tified abnormal actin-interacting protein 1 (Aip1), encoded by WDR1, in patient samples.

103 nd the GAP activity of AIP1 are critical for AIP1-enhanced ASK1 activation.

104 Recruited AIP1 enhances ASK1-induced JNK activation, and the ASK1

105 We predict the C-terminus of Aip1 enhances defective chemotaxis of Ddnhe1(-) cells by

106 ics, whereas in the presence of ADF/cofilin, AIP1 enhances filament fragmentation by capping ends of

107 Actin-interacting protein 1 (AIP1) enhances fragmentation of ADF/cofilin-bound filame

108 nal fragment of actin-interacting protein 1 (Aip1) enhances the chemotaxis defect of Ddnhe1(-) cells

109 AIP1 exists in a closed form through an intramolecular i

110 1, our current data suggest that full-length Aip1 facilitates F-actin assembly when cofilin activity

111 MF cooperates with the Drosophila homolog of Aip1 (flare) in promoting disassembly of Arp2/3-nucleate

112 Xenopus Aip1 forms a cofilin-dependent cap at filament barbed en

113 Yeast Aip1 forms a cofilin-dependent filament barbed end cap,

114 important implications for the structure of Aip1 from other organisms and WD repeat-containing prote

115 TNF binding induces release of AIP1 from TNFR1, resulting in cytoplasmic translocation

116 AIP1 functions as a negative regulator in IFN-gamma-indu

117 We conclude that AIP1 functions as a novel Arf6-GAP to negatively regulat

118 Taken together, our data demonstrate that AIP1 functions as an endogenous inhibitor in VEGFR2-medi

119 ALIX/AIP1 functions in enveloped virus budding, endosomal pro

120 However, how AIP1 functions in the cellular actin cytoskeletal dynami

121 Aip1 functions to promote cofilin-dependent actin remode

122 We previously reported that unc-78, an AIP1 gene in the nematode Caenorhabditis elegans, is req

123 Deletion of the AIP1 gene is lethal in combination with cofilin mutants

124 Here we report that a second AIP1 gene, aipl-1 (AIP1-like gene-1), has overlapping fu

125 Studies in model organisms demonstrated that AIP1 genetically interacts with ADF/cofilin and particip

126 Actin-interacting protein 1 (AIP1) has emerged as a conserved WD-repeat protein that

127 ained elusive; however, Coronin, Cofilin and AIP1 have been implicated in this process.

128 o acids 796-807) is critical for maintaining AIP1 in a closed form, which associates with a region of

129 Knock-out of AIP1 in cells increases and overexpression of AIP1 reduc

130 dicate that the actin-regulating activity of AIP1 in cooperation with ADF/cofilin is essential for it

131 gnaling cascade, we investigated the role of AIP1 in ER stress-induced signaling.

132 servations suggest a potential role for ALIX/AIP1 in linking Mopeia virus NP to Z and the budding app

133 knockdown ECs, suggesting a critical role of AIP1 in recruiting PP2A to ASK1.

134 The role of AIP1 in VSMCs and VSMC proliferative disease is not know

135 Mechanistically, knockout or knockdown of AIP1 in VSMCs significantly enhanced IFN-gamma-induced J

136 Aip1 increases up to 12-fold the rate that high concentr

137 Aip1 inhibits elongation of aged ADP-actin filaments dec

138 co-immunoprecipitation experiments, SETA and AIP1 interacted and could form a complex with apoptosis-

139 However, the mechanism by which AIP1 interacts with ADF/cofilin and actin is not clearly

140 ermore, we show that the Bro1 domain of ALIX/AIP1 interacts with the NP and Z proteins simultaneously

141 Further, AIP1 interacts with Tsg101 and homologs of a subunit of

142 d neointima formation, an effect reversed in AIP1/interferon-gamma receptor (IFN-gammaR) doubly-defic

143 Aip1 inverts the rules of cofilin-mediated actin disasse

144 AIP1-IRE1 association facilitates IRE1 dimerization, a c

145 ER stress induced formation of an AIP1-IRE1 complex, and the PH domain of AIP1 is critical

146 Our results indicate that Aip1 is a cofilin-dependent actin depolymerization facto

147 Alix/AIP1 is a multifunctional adaptor protein that participa

148 Thus, AIP1 is a new class of actin regulatory proteins that se

149 We further show that AIP1 is a novel GTPase-activating protein (GAP) for Arf6

150 Taken together, our data suggest that AIP1 is a novel transducer in TNF-induced TRAF2-dependen

151 We report that AIP1 is a single-copy gene in the moss Physcomitrella pa

152 Alix/AIP1 is an adaptor protein involved in regulating the fu

153 Thus, AIP1 is an important regulator of actin filament organiz

154 f an AIP1-IRE1 complex, and the PH domain of AIP1 is critical for the IRE1 interaction.

155 that a TNF-inducible 14-3-3-binding site on AIP1 is critical for the opening of its conformation and

156 AIP1 is diffusely cytosolic and functions in a common ge

157 Our data suggest that AIP1 is essential for the normal functioning of the acti

158 We conclude that AIP1 is essential for transducing the IRE1-mediated ER s

159 Sequence alignment shows that AIP1 is highly similar to BRO1, a yeast protein related

160 , we show that the cofilin accessory protein Aip1 is important for establishment of normal actin mono

161 tion is significantly blunted in cells where AIP1 is knocked down by RNA interference.

162 Here we show that AIP1 is localized on the plasma membrane in resting endo

163 chanism by which TNF signaling is coupled to AIP1 is not known.

164 We present mechanistic data that suggest AIP1 is recruited to the VEGFR2-PI3K complex, binding to

165 Actin interacting protein 1 (Aip1) is a conserved component of the actin cytoskeleton

166 DF)/cofilin and actin-interacting protein 1 (AIP1) is a conserved mechanism to promote reorganization

167 Actin-interacting protein 1 (AIP1) is a WD40 repeat protein that enhances actin filam

168 In particular, actin interacting protein 1 (AIP1) is capable of capping F-actin and enhancing the ac

169 iated protein 9, ARA9 (also known as XAP2 or AIP1), is a chaperone that is found in complexes with ce

170 n with unc-78, and that depletion of the two AIP1 isoforms causes embryonic lethality.

171 wn, with the enhanced EC migration caused by AIP1 knockdown being associated with increased VEGFR2 si

172 ociation of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a critical role of AIP1 i

173 expression, whereas it was augmented by both AIP1 knockout and knockdown, with the enhanced EC migrat

174 Consistent with a role in actin remodeling, AIP1 knockout lines accumulate F-actin bundles, have few

175 AIP1 knockout plants are viable but have reduced expansi

176 mouse IFN-gamma transgene, donor grafts from AIP1-knockout mice enhanced IFN-gamma-induced VSMC proli

177 transplantation model in which wild-type or AIP1-knockout mouse aortas were transplanted into IFN-ga

178 AIP1-KO cells show dramatic reductions in ER stress-indu

179 Furthermore, reconstitution of AIP1-KO cells with AIP1 wild type, not an AIP1 mutant wi

180 , but not the PERK-CHOP1 axis, is blunted in AIP1-KO cells.

181 More importantly, AIP1-KO mice show impaired ER stress-induced IRE1-depend

182 We created AIP1-deficient mice (AIP1-KO) from which mouse embryonic fibroblasts and vasc

183 terminus, and TNF-alpha induces unfolding of AIP1 leading to association of AIP1 with ASK1.

184 e we report that a second AIP1 gene, aipl-1 (AIP1-like gene-1), has overlapping function with unc-78,

185 Together, coronin and Aip1 lower the amount of cofilin required to disassemble

186 therefore, recognition of the cyclic form of AIP1 may be necessary for antibody-mediated neutralizati

187 the opening of its conformation and for the AIP1-mediated TNF signaling.

188 These data suggest that AIP1 mediates TNF-alpha-induced ASK1 activation by facil

189 However, expression of full-length Aip1 mostly suppresses chemotaxis defects of Ddnhe1(-) c

190 We also found that a dominant negative (DN) AIP1 mutant inhibited production and/or release of envel

191 of AIP1-KO cells with AIP1 wild type, not an AIP1 mutant with a deletion of the PH domain (AIP1-Delta

192 An AIP1 mutant with deletion of this proline-rich region co

193 on in yeast where cofilin is essential while aip1 mutations result in only subtle defects in the acti

194 conserved adaptor protein Alix, also called AIP1 or Hp95, promotes flattening and alignment of cultu

195 , VEGF-induced EC migration was inhibited by AIP1 overexpression, whereas it was augmented by both AI

196 GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation a

197 Our results demonstrate that RIP1-mediated AIP1 phosphorylation at the 14-3-3-binding site Ser-604

198 different protein-protein interactions, with AIP1 playing a key role in linking complexes that act ea

199 t a model in which this conserved surface of AIP1 plays a direct role in enhancing fragmentation/depo

200 now shows that the ASK1-interacting protein, AIP1, plays an important role in TNF-alpha-induced ASK1

201 Endogenous AIP1-PP2A complex can be detected in the resting state,

202 tate, and TNF induces a complex formation of AIP1-PP2A with ASK1.

203 We provide the first demonstration that Aip1 promotes actin turnover in living cells.

204 Importantly, we demonstrate that AIP1 promotes and ADF is essential for cortical F-actin

205 Overexpression of a truncated form of AIP1 protects two different cell types from death induce

206 ctin filament disassembly by ADF/cofilin and AIP1 proteins is critical for embryogenesis.

207 Endogenous SETA and AIP1 proteins showed similar patterns of staining in pri

208 IP1 in cells increases and overexpression of AIP1 reduces cellular PIP(2) levels.

209 lates to human disease, vaccine targeting of AIP1-regulated virulence could have a major clinical imp

210 It has been previously reported that Aip1 regulates cofilin-mediated actin depolymerization,

211 n partially compensate for loss of AIP1, and AIP1 requires ADF for function.

212 Consistent with this model, deletion of AIP1 rescues the temperature-sensitive growth and loss o

213 We suggest that the reduction in AIP1 results in a decrease in F-actin turnover and the p

214 Thus, deletion of the GAP domain on AIP1 results in a loss of its ability to mediate the inh

215 The crystal structure of AIP1 revealed its unique structure with two seven-bladed

216 ze the effect of the inducible expression of AIP1 RNAi in Arabidopsis plants to assess AIP1s role in

217 Overexpression of AIP1-S604A blocks TNF-induced ASK1-JNK activation.

218 Mutation of AIP1 at Ser-604 (AIP1-S604A) blocks TNF-induced complex formation of AIP1

219 thermore, RIP1 synergizes with AIP1 (but not AIP1-S604A) in inducing both JNK/p38 activation and EC a

220 ctions with TRAF2 and ASK1 do not occur with AIP1-S604A, suggesting that phosphorylation at this site

221 the interaction between endogenous SETA and AIP1 sensitizes astrocytes to apoptosis in response to D

222 perative activities of cofilin, coronin, and Aip1 should provide a biochemical basis for understandin

223 Vaccination with PP7-AIP1S elicited AIP1-specific antibodies and limited agr-activation in v

224 Furthermore, AIP1 specifically bound to JAK2 and inhibited its activi

225 ADF/cofilin severed filaments and AIP1 strongly enhanced disassembly at nanomolar concentr

226 n of a ubiquitous actin-interacting protein, Aip1, suggested to work with cofilin.

227 Through systematic mutagenesis of Aip1 surfaces, we identify two well-separated F-actin-bi

228 ace revealed hyperactive alleles of cof1 and aip1 that support the ternary complex model and suggest

229 Aip1 therefore offers a potential control point for disa

230 s 14-3-3 and thioredoxin and synergizes with AIP1 to induce ASK1 activation.

231 At the same time, the binding of AIP1 to TRAF2 inhibits TNF-induced IKK-NF-kappaB signali

232 ously shown that ASK1-interacting protein 1 (AIP1) transduces tumor necrosis factor-induced ASK1-JNK

233 crystal structure of Caenorhabditis elegans AIP1 (UNC-78), which revealed 14 WD40 modules arranged i

234 AIP1 via its pleckstrin homology and C2 domains binds to

235 Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to th

236 Barbed end capping by ADF/cofilin and AIP1 was weak and allowed filament elongation, whereas g

237 Ser-604, located in the C-terminal domain of AIP1, was identified as a 14-3-3-binding site.

238 ecting distinct antiparallel beta-strands of Aip1 were identified in all patients.

239 in concert with actin interacting protein 1 (Aip1), which serves to accelerate cofilin's activity.

240 that the SETA/CIN85-interacting protein Alix/AIP1, which also binds endophilins, modulates this compl

241 Finally, the proteins ADF and AIP1, which both mediate actin filament severing, contri

242 main near the C terminus of p6 binds to ALIX/AIP1, which functions in the same endosomal sorting path

243 Cof1 in turn recruits AIP1, which rapidly triggers severing and remains bound

244 ermore, reconstitution of AIP1-KO cells with AIP1 wild type, not an AIP1 mutant with a deletion of th

245 04A) blocks TNF-induced complex formation of AIP1 with 14-3-3.

246 Interaction of AIP1 with actin was originally characterized by a yeast

247 unfolding of AIP1 leading to association of AIP1 with ASK1.

248 NF treatment normally induces association of AIP1 with TRAF2-ASK1.

249 ging, we show that mammalian Cor1B, Cof1 and AIP1 work in concert through a temporally ordered pathwa