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 le mechanism behind the enhanced severing by AIP1.

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

5 was markedly diminished by overexpression of AIP1.

6 particularly toward its pro-apoptotic target AIP1.

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

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

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

10 timal expansion to determine the function of AIP1.

11 eing necessary for its interaction with ALIX/AIP1.

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

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

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

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

16 n, cofilin, and actin-interacting protein 1 (AIP1) act in synergy to promote rapid F-actin network di

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

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

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

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

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

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

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

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

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

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

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

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

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

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

31 AIP1 alone has negligible effects on actin filament dyna

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

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

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

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

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

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

38 Cofilin and actin-interacting protein 1 (AIP1; also known as WDR1) are evolutionally conserved pr

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

40 1 binds to ALG-2 interacting protein X (Alix/AIP1), an interactor of apoptosis-linked gene protein 2

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

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

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

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

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

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

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

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

49 In this "molecular squeezing" mechanism, AIP1 and not cofilin is responsible for filament severin

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

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

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

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

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

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

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

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

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

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

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

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

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

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

64 , tropomyosin, capping protein, cofilin, and AIP1) are sufficient to reconstitute the formation of ca

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

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

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

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

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

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

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

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

73 -604 is essential for TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of AS

74 3-3 associates with an open, active state of AIP1 assessed by an in vitro pulldown assay.

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

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

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

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

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

80 Aip1 attacks these hypertwisted regions along their side

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

82 AIP1 binding and severing were detected preferentially a

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

84 After AIP1 binding to a filament, severing occurred with a del

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

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

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

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

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

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

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

92 (cofilin, GMF, twinfilin, Srv2/CAP, coronin, AIP1, capping protein, and profilin) work in concert to

93 llaborative effects of Cofilin, Coronin, and AIP1 (CCA).

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

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

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

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

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

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

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

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

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

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

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

105 hat the combination of cofilin, coronin, and Aip1 disassembled filaments in bursts.

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

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

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

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

110 le kinetic analyses of fluorescently labeled AIP1 during the severing process of cofilin-decorated ac

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

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

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

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

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

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

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

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

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

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

121 AIP1 exists in a closed form through an intramolecular i

122 1, our current data suggest that full-length Aip1 facilitates F-actin assembly when cofilin activity

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

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

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

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

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

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

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

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

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

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

133 Aip1 functions to promote cofilin-dependent actin remode

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

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

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

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

138 (Tpm1> Pfy1> Cof1> Abp1> Srv2> Abp140> Tpm2> Aip1> Cap1/2> Crn1> Sac6> Twf1> Arp2/3> Scp1).

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

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

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

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

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

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

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

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

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

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

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

150 Aip1 inhibits elongation of aged ADP-actin filaments dec

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

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

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

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

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

156 Aip1 inverts the rules of cofilin-mediated actin disasse

157 AIP1-IRE1 association facilitates IRE1 dimerization, a c

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

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

160 Alix/AIP1 is a multifunctional adaptor protein that participa

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

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

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

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

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

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

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

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

169 AIP1 is diffusely cytosolic and functions in a common ge

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

188 AIP1 knockout plants are viable but have reduced expansi

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

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

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

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

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

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

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

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

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

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

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

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

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

202 tics of binding and dissociation of a single AIP1 molecule to/from actin filaments followed a second-

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

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

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

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

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

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

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

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

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

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

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

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

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

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

217 Coronin and Aip1 promote cofilin-mediated actin filament disassembly

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

243 d molecular actions of coronin, cofilin, and AIP1 that lead to actin filament aging and severing.

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

245 Aip1 therefore offers a potential control point for disa

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

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

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

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

250 AIP1 via its pleckstrin homology and C2 domains binds to

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

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

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

254 s is mainly achieved by cofilin, assisted by Aip1/Wdr1 and coronins.

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

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

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

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

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

260 actin serves as a high-affinity platform for AIP1, which induces severing by acting as a clamp that d

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

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

263 04A) blocks TNF-induced complex formation of AIP1 with 14-3-3.

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

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

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

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