ライフサイエンスコーパス: PBX1

1 pre-B-cell leukemia transcription factor-1 (PBX1).

2 imerize with pre-B-cell leukemia homeobox-1 (Pbx1).

3 be activated cooperatively by Klf4 and Meis2/Pbx1.

4 eins but not by the leukemic oncoprotein E2a-Pbx1.

5 evelopment more severely than single loss of Pbx1.

6 d deletions and loss of function variants in PBX1.

7 Wnt16 has been shown to be targeted by E2A-Pbx1.

8 g but independent of direct interaction with PBX1.

9 e homeodomain proteins, which includes human Pbx1.

10 entiation and function in mice deficient for Pbx1.

11 ssion that includes the transcription factor Pbx1.

12 binding to the common heterodimeric partner Pbx1.

13 s1, decreasing its stability by sequestering Pbx1.

14 g KIX and bone marrow immortalization by E2A-PBX1.

15 Pbx1/2 mutants have three salient molecular phenotypes o

16 ations/deletions in the PBX homeobox 1 gene (PBX1), a gene known to have a crucial role in kidney dev

17 Pbx1, a homeodomain transcription factor that was origin

18 In this study, we have identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a

19 This study suggests that perturbation of Pbx1 activity may also promote susceptibility to diabete

20 osteocalcin and Bsp promoters revealed that Pbx1 acts through a Pbx-binding site that is required to

21 Hoxd3(-/-) compound mutants, suggesting that Pbx1 acts together with multiple Hox proteins in the dev

22 Pbx1+/- adults had pancreatic islet malformations, impai

23 hat decreasing Pbx2 dosage in the absence of Pbx1 affects axial development more severely than single

24 (SLC19A1, an MTX uptake transporter) in E2A-PBX1 ALL, significantly higher expression of breast canc

25 ges of differentiation, similar to human E2A-PBX1 ALL.

26 Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endot

27 E2a-Pbx1, an oncogenic derivative of Pbx1, both retains its

28 iral transcription whereas overexpression of PBX1 and a PBX1-associated protein, PREP1, enhanced vira

29 Pbx1 and a subset of homeodomain proteins collaborativel

30 diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others.

31 posterior HOX protein, HoxA9, complexed with Pbx1 and DNA, which reveals that the posterior Hox hexap

32 We demonstrate that Pbx1 and Emx2 bind in vivo to a conserved sequence upstr

33 bx1;Emx2 genetic interaction by showing that Pbx1 and Emx2 can bind specific DNA sequences as heterod

34 a analysis, we provide new insight into TCF3-PBX1 and ETV6-RUNX1 acute lymphoblastic leukemia.

35 ervation prompts the question of whether E2a-Pbx1 and Hox oncoproteins use endogenous Hox and Pbx pro

36 Pbx1 and Hox11 genetically interact in spleen formation

37 n spleen mesenchymal cells, which co-express Pbx1 and Hox11.

38 Chromatin-associated Pbx1 and Hoxa10 were present at osteoblast-related gene

39 evealed in vivo genetic interactions between Pbx1 and Ipf1 that are essential for postnatal pancreati

40 Thus, our results reveal novel roles for PBX1 and its transcriptional network in mDAn development

41 ites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf

42 rogenitors exhibit elevated levels of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, a

43 We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 a

44 Notably, PBX1 and NFE2L1 levels are severely reduced in dopaminer

45 Moreover, Pbx1 and Oct-1, as well as Prep1 and Oct-1, form functio

46 In this study, we first uncover that Pbx1 and Pbx2 are co-expressed in the lateral plate and

47 tion, Pax6 expression becomes dependent upon Pbx1 and Pbx2 function.

48 In addition, analysis of Pbx1 and Pbx2 knockout mice demonstrates that, during pa

49 In the absence of Pbx1 and Pbx3 function, Hox-dependent programs are lost

50 oles recently established for family members Pbx1 and Pbx3.

51 ole of two developmentally critical factors (Pbx1 and Prep-1) in the regulation of homeostasis in the

52 demonstrating that the homeodomain proteins PBX1 and PREP1 are cellular factors involved in Moloney

53 conserved binding sites for Klf4, Meis2, and Pbx1 and show that at least some of these genes can be a

54 bly lower levels than comparable isoforms of Pbx1 and/or Pbx3 in embryonic tissues.

55 repressor of pre-B-cell leukemia homeobox 1 (PBX1) and is also known to regulate estrogen receptor fu

56 pre B-cell leukemia transcription factor 1 (PBX1) and PBX-regulating protein-1 (PREP1), function as

57 late cortical patterning (CoupTFI, Pax6, and Pbx1), and analysis of enhancer activity in Pax6 mutants

58 tion factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in m

59 pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously undetected d

60 4 methyltransferase, is required for FOXA1, PBX1, and ER recruitment and activation.

61 onstrate that Gfi1 directly represses HoxA9, Pbx1, and Meis1 during normal myelopoiesis.

62 nscription factors Run1t1, Hlf, Lmo2, Prdm5, Pbx1, and Zfp37 imparts multilineage transplantation pot

63 Pbx1, another Meis1 cofactor, also induces apoptosis; ho

64 ncluded the genetic abnormality t(1;19)(TCF3-PBX1), any CNS involvement at diagnosis, and T-cell immu

65 f Pax6 and further demonstrate that Msx2 and Pbx1 are bona fide direct regulators of early Six3.2 dis

66 Both FRA-1 and PBX1 are required for the mesenchymal changes triggered

67 quence requirements for binding by Meis2 and Pbx1 are variable.

68 In addition, our results identify Pbx1 as a novel regulator of CD4(+) T cell effector func

69 ription whereas overexpression of PBX1 and a PBX1-associated protein, PREP1, enhanced viral transcrip

70 c lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL translocations and trisomies of

71 ssues or isolated cells, we further detected PBX1 binding to known regulatory regions of the neuron-s

72 romatin immunoprecipitation assays show that Pbx1 binds to the Hox11 promoter in spleen mesenchymal c

73 E2a/Pbx1 blocks differentiation of primary myeloid progenito

74 E2a-Pbx1, an oncogenic derivative of Pbx1, both retains its ability to heterodimerize with Ho

75 Mechanistically, E2A-PBX1 bound promoter regulatory regions and activated the

76 d HoxA9-mediated CYBB-transcription requires Pbx1 but is inhibited by Meis1.

77 Targeted deletion of Pbx1 by retroviral transduction of Cre recombinase into

78 Conversely, targeted depletion of Pbx1 by short hairpin RNA (shRNA) increased expression o

79 revious analysis of the in vivo functions of Pbx1 by targeted mutagenesis in mice has revealed roles

80 Pbx1 can, therefore, alternatively act as an oncogene or

81 nclude that deleterious sequence variants in PBX1 cause intellectual disability and pleiotropic malfo

82 hIP-BIT to find target genes from NOTCH3 and PBX1 ChIP-seq data acquired from MCF-7 breast cancer cel

83 nchymal cells and identified components of a Pbx1 complex associated with genes in osteoblasts.

84 Pbx1 contributions were investigated through characteriz

85 Here, we show that PBX1 controls a novel transcriptional network required f

86 Pbx1 controls chromatin accessibility to a large number

87 E2a-Pbx1 cooperated with cytokines or activated signaling on

88 mias induced by the chimeric oncoprotein E2a-Pbx1 created by t(1;19) chromosomal translocations.

89 Thus, Pbx1 critically functions at a stage between hematopoiet

90 64, CD304, CD97, CD102, CD99, CD300a, CD130, PBX1, CTNNA1, ITGB7, CD69, CD49f) were differentially ex

91 Pre-B cell leukemia homeobox 1 (Pbx1)-d is a dominant-negative splice isoform of the gen

92 rate that Sle1a1 MSCs express high levels of Pbx1-d as compared with congenic C57BL/6J (B6) MSCs.

93 The Pbx1-d dominant-negative isoform is more frequent in CD4

94 tested the hypothesis that the expression of Pbx1-d favors MSC differentiation and impairs their immu

95 Our results suggest that Pbx1-d impacts lupus development by regulating effector

96 Transgenic (Tg) expression of Pbx1-d in CD4(+) T cells reproduced the phenotypes of Sl

97 Pbx1-d is associated with the production of autoreactive

98 PBX1-d is expressed more frequently in the CD4(+) T cell

99 xpression of the lupus susceptibility allele Pbx1-d isoform impairs MSC functions, which may contribu

100 Pbx1-d overexpression is sufficient to induce an activat

101 Moreover, Pbx1-d-Tg CD4(+) T cells upregulated the expression of m

102 Pbx1-d-Tg expression also expanded the number of follicu

103 xpression of a novel splice isoform of Pbx1, Pbx1-d.

104 , reducing expression of endogenous Meis2 or Pbx1 decreases p15 gene expression and increases the num

105 Pbx1 deficiency also results in the failure of cardiac O

106 We previously reported that Pbx1 deficiency causes organ growth defects including as

107 drocyte differentiation was not perturbed in Pbx1-deficient cartilage at early days of embryonic skel

108 s following restoration of its expression in Pbx1-deficient ES cells.

109 ransfer experiments, B-cell development from Pbx1-deficient fetal liver cells was also severely compr

110 ere investigated through characterization of Pbx1-deficient mice.

111 ) embryos was conducted to further elucidate Pbx1-dependent processes during organogenesis.

112 ously reported, Pbx1 homozygous mutant mice (Pbx1-/-) develop malformations and hypoplasia or aplasia

113 We show that Pbx1 directly activates Pax3, leading to repression of i

114 Notably, we establish that Pbx1 directly represses Pdgfrb, and demonstrate that dec

115 pt these interactions, destabilize the HOXB1:PBX1:DNA complex, and alter HOXB1 transcriptional activi

116 ns-ETV6-RUNX1 (TEL-AML1), BCR-ABL1, and TCF3-PBX1 (E2A-PBX1)-frequently found in precursor-B-cell acu

117 ricted progenitors, are markedly depleted in Pbx1(-/-) embryos at E14 and display clonogenic defects

118 Prior to death at E15.5, Pbx1(-/-) embryos displayed kidneys that were reduced in

119 Hematopoietic stem cells from Pbx1(-/-) embryos have reduced colony-forming activity a

120 y, examination of metanephric development in Pbx1(-/-) embryos was conducted to further elucidate Pbx

121 Pbx1-/- embryos had pancreatic hypoplasia and marked def

122 Analyses of Pbx and Pbx1;Emx2 compound mutants revealed that Pbx genes share

123 Here, we provide a biochemical basis for Pbx1;Emx2 genetic interaction by showing that Pbx1 and E

124 Pbx1 encodes a TALE homeodomain transcription factor tha

125 PBX1 encodes a three amino acid loop extension (TALE) ho

126 port here that experimental induction of E2a-Pbx1 enhances expression of BMI-1, a lymphoid oncogene w

127 ence further maturation, suggesting that E2a/Pbx1 establishes an early block in pro-T-cell developmen

128 w progenitors with an estrogen-regulated E2a/Pbx1-estrogen receptor fusion protein.

129 We find that PTBP1 represses Pbx1 exon 7 and the expression of the neuronal Pbx1a iso

130 Loss of Pbx1 expression in neuronally committed neuroblasts in t

131 Pbx1 expression is transcriptionally regulated by Notch3

132 lopment and function, we examined pancreatic Pbx1 expression, and morphogenesis, cell differentiation

133 bitor could be partially reversed by ectopic Pbx1 expression.

134 moter (Cd19, Mb1, or Mx1) used to induce E2A-PBX1 expression.

135 Pbx1(f/f) mice were crossed with mice containing Cre rec

136 itive myeloerythroid lineages are present in Pbx1(-/-) fetal livers, but the total numbers of colony-

137 NX1 (TEL-AML1), BCR-ABL1, and TCF3-PBX1 (E2A-PBX1)-frequently found in precursor-B-cell acute lymphob

138 Loss of Pbx1 from osteoblast promoters in differentiated osteobl

139 ered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal tra

140 nt machinery as a direct target for the TCF3-PBX1 fusion protein.

141 e t(1;19) chromosomal translocation with E2A-PBX1 fusion, and were less likely to have hyperdiploid b

142 at B-lineage ALL with either TEL-AML1 or E2A-PBX1 gene fusion, or T-lineage ALL, accumulates signific

143 ically deregulated after ETV6-RUNX1 and TCF3-PBX1 gene fusions, respectively.

144 e novo, deleterious sequence variants in the PBX1 gene.

145 pre-B-cell leukemia transcription factor 1 (Pbx1) gene, down-regulated by CDKI treatment.

146 ranslocation yields a fusion between E2A and PBX1 genes and occurs in 5% of acute lymphoblastic leuke

147 g functions in shoulder development and that Pbx1 genetically interacts with Emx2 in this process.

148 ol spleen development via separate pathways, Pbx1 genetically regulates key players in both pathways,

149 eduction or absence of Pbx2 or Pbx3 leads to Pbx1 haploinsufficiency and specific malformations that

150 l lines, and no transforming function of E2a/Pbx1 has been reported in cultured lymphoid progenitors.

151 The TALE homeoprotein Pbx1 has been shown to be essential for proximal limb de

152 ns, or a yet undefined factor that binds the Pbx1 HD and derepresses DNA-binding by the HD, cooperate

153 luded missense substitutions adjacent to the PBX1 homeodomain (p.Arg184Pro, p.Met224Lys, and p.Arg227

154 r cells, are absent in the splenic anlage of Pbx1 homozygous mutant (-/-) embryos, implicating the TA

155 As previously reported, Pbx1 homozygous mutant mice (Pbx1-/-) develop malformati

156 Pbx1 homozygous mutants exhibited delayed or absent form

157 itors are resistant to transformation by E2a-Pbx1; however, the requirement for Bmi-1 is alleviated i

158 ic mice mutant for the transcription factors Pbx1, Hox11 (Tlx1), Nkx3.2 (Bapx1) and Pod1 (capsulin, T

159 These studies establish a Pbx1-Hox11-dependent genetic and transcriptional pathway

160 Expression of Pbx1 impaired osteogenic commitment of C3H10T1/2 multipo

161 sequenced the genomic fusion between E2A and PBX1 in 22 preB acute lymphoblastic leukemias and two ce

162 Somatic activation of E2A-PBX1 in B cell progenitors enhanced self-renewal and led

163 tudies have demonstrated a critical role for Pbx1 in cellular proliferation and patterning and sugges

164 iation, suggesting an important function for Pbx1 in determining corneal identity.

165 division, as inactivation of conditional E2a/Pbx1 in either factor-dependent pro-T cells or pro-T cel

166 Our results establish an essential role for Pbx1 in genetic interactions with its family members and

167 An obligatory role for Pbx1 in limb axis patterning was apparent from malformat

168 en together, these data establish a role for Pbx1 in mesenchymal-epithelial signaling and demonstrate

169 Despite the restricted expression of Pbx1 in metanephric mesenchyme, developing nephrons, and

170 These studies demonstrate a role for Pbx1 in multiple developmental programs and reveal a nov

171 es DNA-binding by the HD, cooperate with E2a-Pbx1 in myeloid immortalization.

172 To investigate in vivo roles of Pbx1 in pancreatic development and function, we examined

173 n studies have suggested a possible role for Pbx1 in pharyngeal region development.

174 ribe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of t

175 Conditional inactivation of Pbx1 in pro-B (CD19(+)) cells and thereafter revealed th

176 al ablation of the TALE transcription factor Pbx1 in renal VMC progenitors in the mouse led to the pr

177 ) embryos, implicating the TALE homeoprotein Pbx1 in splenic cell specification.

178 Tissue-specific deletion of Pbx1 in the corneal epithelium of mice resulted in corne

179 e investigated the potential requirement for Pbx1 in the development of the pharyngeal arches and pou

180 Expression of the PBC protein PBX1 in the SVZ has been reported, but its functional ro

181 Here, we present evidence that Pbx1, in partnership with Meis1b, can regulate posterior

182 w that mice with splenic mesenchyme-specific Pbx1 inactivation exhibit hyposplenia.

183 we identify HoxA10 amino acids 224-249 as a Pbx1-independent repression domain, which interacts with

184 functions of Hox proteins in this region are Pbx1-independent.

185 interaction as a therapeutic target for E2A-PBX1-induced leukemia.

186 Here, we demonstrate that E2a/Pbx1 induces immortal proliferation of stem cell factor

187 emia homeobox interacting protein 1 or human PBX1 interacting protein (PBXIP1/HPIP) is a co-repressor

188 Breakpoints on the 232-kb PBX1 intron 1 were more dispersed but highly clustered p

189 Analysis of trans-heterozygous Pbx1+/- Ipf1+/- mice revealed in vivo genetic interactio

190 n together, the above findings indicate that Pbx1 is a direct Notch3-regulated gene that mediates the

191 Pbx1 is a homeodomain protein that functions in complexe

192 Pbx1 is a member of the TALE (three-amino acid loop exte

193 These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates

194 Pbx1 is a TALE-class homeodomain protein that functions

195 ss-of-function mouse model, we now show that Pbx1 is an early regulator of SVZ neurogenesis.

196 al-epithelial signaling and demonstrate that Pbx1 is an essential regulator of mesenchymal function d

197 Our results show that Pbx1 is associated with histone deacetylases normally li

198 y inactive genes: In undifferentiated cells, PBX1 is bound to the H1-compacted promoter/proximal enha

199 y Pbx1 short hairpin RNA knockdown show that Pbx1 is essential for cell proliferation and tumorigenic

200 Thus, Pbx1 is essential for normal pancreatic development and

201 Taken together, these data indicate that Pbx1 is essential for the function of hematopoietic prog

202 Finally, Pbx1 is expressed in GnRH neurons in embryonic as well a

203 This paper reports that Pbx1 is expressed in hematopoietic progenitors during mu

204 These findings suggest that PBX1 is involved in monogenic CAKUT in humans and call i

205 (CD19(+)) cells and thereafter revealed that Pbx1 is not necessary for B-cell development to proceed

206 Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocatio

207 Thus, Pbx1 is required for the maintenance, but not the initia

208 Pbx1 is required to maintain stem cell self-renewal, inc

209 Pbx1 is the product of a proto-oncogene originally disco

210 nduction of tubulogenic mesenchyme; however, Pbx1(-/-) kidneys contained fewer nephrons and were char

211 the lymphoid versus myeloid character of E2a/Pbx1 leukemia and may cooperate with E2a/Pbx1 to dictate

212 example, whereas the E2A portion of the E2A-Pbx1 leukemia fusion protein mediates robust transcripti

213 ation of mouse and human ALLs, including E2A-PBX1 leukemias, and increased disease-free survival afte

214 oliferation of human and mouse preBCR(+)/E2A-PBX1(+) leukemias in vitro and in vivo Furthermore, comb

215 Thus, Pbx1 makes a crucial contribution to distinct regulatory

216 ia (ALL) and four ALL subtypes: BCR-ABL, E2A-PBX1, MALL and TALL.

217 es, HES-5, HEY-1, c-Myc, Deltex-1, NRARP and PBX1, markedly increased in MARY-X.

218 of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and progenitor transformation in co

219 differentiation; the suppression of a HoxA9-Pbx1-Meis1 progenitor program and the induction of a gra

220 These data support conditional E2A-PBX1 mice as a model of human ALL and suggest targeting

221 program of SVZ neurogenesis, suggesting that PBX1 might act as a priming factor to mark these genes f

222 to be limited to few ALL subtypes (e.g. TCF3-PBX1), most mature B-cell lymphomas rely on BCR signalin

223 leiotropic malformations resembling those in Pbx1 mutant mice, arguing for strong conservation of gen

224 However, some aspects of the Pbx1 mutant phenotype included specific defects that wer

225 Pbx1 mutants died at embryonic day 15/16 with severe hyp

226 that decreased Pdgfrb dosage in conditional Pbx1 mutants substantially rescues vascular patterning d

227 Here we have established that Pbx1 negatively regulates Hoxa10-mediated gene transcrip

228 complementation assays, we demonstrate that Pbx1 null embryonic stem (ES) cells fail to generate com

229 Pbx1-null embryos display anomalous great arteries owing

230 Compound Msx2/Pbx1-null embryos display significant rescue of cardiac

231 Pbx1-null embryos lose a transient burst of Pax3 express

232 the great-artery anomalies of compound Msx2/Pbx1-null embryos remain within the same spectrum as tho

233 remain within the same spectrum as those of Pbx1-null embryos.

234 thway partially underlies the OFT defects in Pbx1-null mice.

235 Furthermore, the adverse effects of E2a-Pbx1 on pre-B cell survival and differentiation are part

236 on 1;19 and consequent expression of the E2A-PBX1 oncoprotein.

237 Here we show that it is PBX3, but not PBX1 or PBX2, that is consistently coexpressed with HOXA

238 own chromosomal translocations (t(1;19)(TCF3-PBX1) or MLL), and 6 of which lacked any previously know

239 ge-dependent overt diabetes mellitus, unlike Pbx1+/- or Ipf1+/- mice.

240 te that the homeodomain transcription factor Pbx1 orchestrates separate transcriptional pathways to c

241 ation, demonstrating that disruption of this Pbx1-Pax3-Msx2 regulatory pathway partially underlies th

242 ased expression of a novel splice isoform of Pbx1, Pbx1-d.

243 Pbx2-deficient (Pbx2(-/-)) embryos, compound Pbx1(-/-); Pbx2(+/-) mutants, in addition to their exace

244 Additionally, we reveal that Pbx1(-/-); Pbx2(-/-) embryos lack limbs altogether.

245 In this study, we uncover that Pbx1/Pbx2 are co-expressed during successive stages of v

246 s, in vertebrates, distal limb patterning is Pbx1/Pbx2 dependent.

247 posterior limb and regulating ZPA function, Pbx1/Pbx2 exert a primary hierarchical function on Hox g

248 By exploiting a Pbx1/Pbx2 loss-of-function mouse model, we demonstrate t

249 Next, by exploiting a Pbx1/Pbx2 loss-of-function mouse, we show that decreasin

250 Pbx1/Pbx2 mutants exhibit a homogeneous vertebral column

251 ulators of notochord signaling are normal in Pbx1/Pbx2 mutants.

252 ing and hindlimb positioning are governed by Pbx1/Pbx2 through their genetic control of Polycomb and

253 ts show how the oncogenic fusion protein E2A-PBX1 perturbs signaling pathways upstream of PLCgamma2 a

254 We propose that Pbx1 plays a central role in attenuating the ability of

255 Mechanistically, PBX1 plays a dual role in transcription by directly repr

256 3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL.

257 g with the stabilization and accumulation of PBX1, PREP1 induces the expression of multiple activator

258 The interaction between the PCE and PBX1-PREP1 proteins was confirmed by gel shift experimen

259 Infusion of E2a/Pbx1 pro-T cells in mice caused T lymphoblastic leukemia

260 In an E2a/Pbx1 pro-T thymocyte clone that induced only pro-T acute

261 h3/CSL protein complex directly binds to the Pbx1 promoter segment harboring the CSL-binding sequence

262 PBX1 protein is expressed throughout murine embryonic de

263 Blocking PBX1 protein synthesis resulted in a significant decreas

264 gesting abnormal interactions between mutant PBX1 proteins and wild-type TALE or HOX cofactors.

265 Retention of myeloid immortalization by E2a-Pbx1 proteins lacking all Pbx1 sequences N- or C-termina

266 r262Glnfs*2, and p.Arg288* yielded truncated PBX1 proteins.

267 e studies establish an essential role of the Pbx1 proto-oncogene in corneal morphogenesis.

268 nduced, MEIS associates with chromatin-bound PBX1, recruits PARP1/ARTD1, and initiates PARP1-mediated

269 Collectively, our results establish that PBX1 regulates adult neural cell fate determination in a

270 In vitro studies have shown that Pbx1 regulates the activity of Ipf1 (also known as Pdx1)

271 Whereas genetic studies indicate that Pbx1 regulates the development and function of insulin-p

272 studies with explant cultures verified that Pbx1(-/-) renal defects arose exclusively from mesenchym

273 T-cell quiescence, while reactivation of E2a/Pbx1 restored cell division.

274 Four further associations at or close to the PBX1, RORalpha, NTN1, and SYT6 loci also came close to g

275 Functional studies on five PBX1 sequence variants revealed perturbation of intrinsi

276 rtalization by E2a-Pbx1 proteins lacking all Pbx1 sequences N- or C-terminal to the HD indicates that

277 Furthermore, functional studies by Pbx1 short hairpin RNA knockdown show that Pbx1 is essen

278 progenitor cells carrying floxed alleles of Pbx1 significantly reduced the production of neurons and

279 ) in P19 cells using both PBX1b-AS cells and PBX1 small interfering RNA.

280 Removal of p15Ink4b in Pbx1 spleen-specific mutants partially rescues spleen gr

281 y was performed to elucidate the role of the Pbx1 TALE protein in the corneal epithelium of mice.

282 tations directly affect the transcription of PBX1 target genes to impact embryonic development.

283 L, including T-cell lineage ALL (T-ALL), E2A-PBX1, TEL-AML1, MLL rearrangements, BCR-ABL, and hyperdi

284 nal transcriptional activation domain of E2A-PBX1, termed the PCET motif, which has previously been i

285 tion site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is

286 dominant-negative splice isoform of the gene Pbx1 that corresponds to the NZM2410 lupus susceptibilit

287 nslocation resulting in a fusion protein E2A-Pbx1 that promotes transformation and leukemogenesis.

288 D1 with HEB-AD1 abolished the ability of E2A-Pbx1 to activate target genes and to induce cell transfo

289 E2a/Pbx1 leukemia and may cooperate with E2a/Pbx1 to dictate the pre-B-cell phenotype of human leukem

290 onditional Pax5 deletion cooperated with E2A-PBX1 to expand progenitor B cell subpopulations, increas

291 Thus, PTBP1 controls the activity of Pbx1 to suppress its neuronal transcriptional program pr

292 All cell lines and primary blasts with E2A-PBX1 translocation and a portion of patients with other

293 ucleotides at the point of fusion in the E2A-PBX1 translocation as well as specific characteristics o

294 patients by screening for the clonotypic E2A-PBX1 translocation in neonatal blood spots, or Guthrie c

295 A critical role for Pbx1 was confirmed by rescue of B-cell development from

296 We observed that the homeodomain factor Pbx1, which cooperates with MyoD to stimulate myogenin e

297 bx2 is expressed throughout the limb, unlike Pbx1, which is expressed only in the proximal bud.

298 leukemias expressing the fusion protein E2A-PBX1, which is present in 5%-7% of pediatric and 50% of

299 However, the protein Pbx1, whose binding site is the best match to one highly

300 A major role is served by Pbx1, whose inactivation results in persistent truncus a

301 These results link E2a-Pbx1 with Bmi-1 on an oncogenic pathway that is likely t

302 monstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/-) sensitization, regulate