ライフサイエンスコーパス: alpha-globin

1 beta-like globin protein that can pair with alpha globin.

2 > Gln) was designed to increase affinity for alpha-globin.

3 advantage over beta(S) for dimerization with alpha-globin.

4 mib did not enhance the accumulation of free alpha-globin.

5 oduction of Hemoglobin A by stabilizing free alpha-globin.

6 e inhibition blocked the degradation of free alpha-globin.

7 interregulated PQC responses degrade excess alpha-globin.

8 has the potential to simultaneously suppress alpha-globin.

9 -globin chain to a highly ordered heme-bound alpha*-globin.

10 bbit HRI and amino acids 16-120 in mammalian alpha-globins.

11 athways exist, especially diversified in the alpha-globins.

12 The unadenylated alpha-globin 3' untranslated region (3'UTR) was an effic

13 s we show that a 26-nucleotide region of the alpha-globin 3'-untranslated region is an autonomous ele

14 rget structure with that of the native human alpha-globin 3'-untranslated region.

15 th alphaCP would be disrupted, rendering the alpha-globin 3'UTR more susceptible to endoribonuclease

16 ins, individually or as a pair, can bind the alpha-globin 3'UTR unless they are complexed with the re

17 ErEN cleavage of an adenylated alpha-globin 3'UTR was accentuated upon depletion of PAB

18 of the three major alphaCP isoforms and the alpha-globin 3'UTR was detected, suggesting that each of

19 ingle alphaCP molecule binds directly to the alpha-globin 3'UTR, resulting in a simple binary structu

20 g an in vitro-transcribed and polyadenylated alpha-globin 3'UTR, we have devised an in vitro mRNA dec

21 nce the binding efficiency of alphaCP to the alpha-globin 3'UTR, which in turn protected the ErEN tar

22 number of proteins were identified including alpha-globin, 6.8 kDa mitochondrial proteolipid, macroph

23 ia, beta-globin synthesis is reduced causing alpha-globin accumulation.

24 nt of Hbb(th1/th1) mice with RAP-536 reduced alpha-globin aggregates in peripheral red cells, decreas

25 sly defined role in detoxification of excess alpha-globin, AHSP also acts as a molecular chaperone to

26 1 of 4 alpha-globin genes (genotype Ahsp(-/-)alpha-globin*(alpha/alphaalpha)) exhibited more severe a

27 e that loss of expression of the major adult alpha-globin, alpha1, in two species of icefish (Chaenoc

28 Alpha globin amino acid substitutions H103Y, H103R, F117

29 emolysates showed that there are three major alpha globins and two beta globins in circulating erythr

30 ng genes, and tissue-specific genes, such as alpha-globin and FMR-1.

31 2)(S)), has been assembled in vitro from pig alpha-globin and human beta(S)-chain.

32 arly demonstrated that direct suppression of alpha-globin and induction of gamma-globin are effective

33 involved in hemoglobin biosynthesis, such as alpha-globin and mitoferrin 1, demonstrating that Hipk2

34 d bone marrow cells, tetramers of two murine alpha-globin and two human betaA-globin molecules accoun

35 icated in the regulation of RNA stability of alpha-globin and tyrosine hydroxylase mRNAs.

36 Nitration on Tyr-24, Tyr-42 (alpha-globin), and Tyr-130 (beta-globin) as well as nitr

37 Employing alpha-globin as a model substrate, we demonstrate the fa

38 thalassemic donors and 3H-alpha-chains or 3H-alpha-globin as a substrate.

39 ngs demonstrate the utility of the expressed alpha-globin as a tool for elucidating the role of this

40 s demonstrated increased levels of insoluble alpha-globin, as well as activated caspase-3.

41 xpressing GATA-1, including those coding for alpha-globin, beta-globin, the erythropoietin receptor,

42 By contrast, K99E and K99N alpha globins bind beta globin normally but exhibit atte

43 lysin), and one was weakly supported (baboon alpha-globin), but two examples (primate lysozyme and An

44 SP aggravates the toxicity of excessive free alpha-globin caused by beta-globin gene disruption in mi

45 nd support the hypothesis that AHSP promotes alpha globin chain stability during human erythropoiesis

46 der of alpha2 beta2 formation under limiting alpha-globin chain conditions showed Hb betaC112S > Hb A

47 f tetramer formation in vitro under limiting alpha-globin chain conditions showed Hb betaG16D, K120E

48 ng protein [AHSP]), which can stabilize free alpha globin chains in vitro, could influence disease se

49 n binding to membranes was assessed and only alpha globin chains were found, in contrast to other uns

50 inherited with beta-thalassemia, excess free alpha-globin chains are reduced significantly ameliorati

51 nd beta-globin chains with an excess of free alpha-globin chains causing ineffective erythropoiesis a

52 s, in turn caused primarily by deposition of alpha-globin chains in erythroid precursors.

53 shown to modulate the accumulation of excess alpha-globin chains in murine beta-thalassemia and to de

54 oglobin, leading to the accumulation of free alpha-globin chains that form toxic aggregates.

55 ta(AS3)-globin monomers compete for limiting alpha-globin chains up to 82% of the tetramers formed is

56 If unlabeled alpha-globin chains were added at the start of chain syn

57 Studies on assembly in vitro of alpha-globin chains with recombinant beta16 Gly-->Asp, b

58 haracterised by the presence of an excess of alpha-globin chains, which contribute to erythrocyte pat

59 ns that are more electropositive than normal alpha-globin chains.

60 ly related to regions rich in membrane-bound alpha-globin chains.

61 roblasts, HSP70 interacts directly with free alpha-globin chains.

62 In addition to delimiting the alpha globin chromosomal domain, this study has enabled

63 cis-acting regulatory elements in the human alpha globin cluster but also demonstrated that there ar

64 iated with such an extensive deletion in the alpha-globin cluster implies that much of the DNA remove

65 oss 130 kb of chromatin containing the mouse alpha-globin cluster in cells representing all stages of

66 emoves a significant proportion of the human alpha-globin cluster including the psizeta1, alpha(D), p

67 Chromatin associated with the alpha-globin cluster is modified by histone methylation

68 itional positive cis-acting sequences in the alpha-globin cluster.

69 latory sequences located far upstream of the alpha-globin cluster.

70 The human alpha-globin complex lies at the tip of the short arm of

71 -specific enhancer activity within the human alpha-globin complex.

72 sequence, IV, were all part of the ancestral alpha-globin-containing unit prior to its tandem duplica

73 t has been suggested that an ancient primate alpha-globin-containing unit was ancestral to the X, Y,

74 b from structural modification by preventing alpha-globin cross-links and oxidations of amino acids i

75 However, it is not clear how alpha-globin deposition causes apoptosis.

76 iple promoters in a mouse model in which the alpha-globin domain is extended to include several addit

77 mbryonic yolk sac to exclusive expression of alpha-globin during fetal and adult life.

78 lar chaperone that binds and stabilizes free alpha-globin during hemoglobin synthesis.

79 nt AHSP promoted folding of newly translated alpha-globin, enhanced its refolding after denaturation,

80 a natural mutation, which deletes the MCS-R2 alpha-globin enhancer and causes alpha-thalassemia.

81 romoter, modified gamma-globin cassette, and alpha-globin enhancer.

82 roach to investigate how interactions of the alpha-globin enhancers are distributed between multiple

83 The review asks how remote elements regulate alpha globin expression and how natural mutations interf

84 Alpha globin expression must be regulated properly to pr

85 own by histology, PECAM1 immunostaining, and alpha globin expression.

86 cells, we observe the expected reduction in alpha-globin expression and a correction of the patholog

87 High-level alpha-globin expression depends on cis-acting regulatory

88 Here the authors use CRISP/Cas9 to reduce alpha-globin expression in hematopoietic precursors, and

89 n positive regulatory element (PRE) activate alpha-globin expression in transgenic mice.

90 ere we review the evidence that reduction of alpha-globin expression may provide an equally plausible

91 However, alpha-globin expression, measured by allele-specific RNA

92 f chromosome 16, coinciding with the loss of alpha-globin expression.

93 mal mental retardation and downregulation of alpha-globin expression.

94 s a molecular chaperone to stabilize nascent alpha-globin for HbA assembly.

95 eta-globins in addition to genetic fusion of alpha-globins further stabilized the hemoglobin molecule

96 A spanning the mouse, chicken and pufferfish alpha globin gene clusters and compared them with the co

97 genes in beta thalassaemia heterozygotes or alpha globin gene deletions in beta thalassaemia homozyg

98 ere were beta homozygotes and 7/8(87.5%) had alpha globin gene deletions.

99 l of the elements required to fully regulate alpha globin gene expression from its natural chromosoma

100 ut a 150 kb chromatin segment containing the alpha globin gene locus as it changes from a poised, sil

101 becoming juxtaposed to a structurally normal alpha-globin gene (HBA2).

102 ne alpha-globin PRE contribute to long-range alpha-globin gene activation.

103 do not localize to a discrete region of the alpha-globin gene and the results of internal deletions

104 whereas nascent transcription from the human alpha-globin gene appears unaffected.

105 ecies, the two paralogs at the 5'-end of the alpha-globin gene cluster (HBA-T1 and HBA-T2) are evolvi

106 Here, using the alpha-globin gene cluster as an illustrative model, we p

107 By replacing the mouse alpha-globin gene cluster in situ with its human counter

108 central developmental event in the human (h)alpha-globin gene cluster is selective silencing of the

109 an association observed between MCH and the alpha-globin gene cluster variants demonstrated independ

110 ions of HBE1 variants with HCT and MCHC, the alpha-globin gene cluster variants with RBC and MCHC, an

111 n of human chromosome 16, which includes the alpha-globin gene cluster, but no molecular defects were

112 and potential regulatory proteins within the alpha-globin gene comprise an intragenic enhancer specif

113 duced by removal of hnRNPH/F both in PLP and alpha-globin gene context.

114 asthma, percentage of fetal hemoglobin, and alpha-globin gene deletion.

115 The human alpha-globin gene expression was at the peak at 3-4 mont

116 pale, and microarray analysis revealed that alpha-globin gene expression was decreased in null versu

117 In the newborn, human alpha-globin gene expression was detected in the liver,

118 ent mice were analyzed after birth for human alpha-globin gene expression.

119 showed low abundance of the transduced human alpha-globin gene in their BFU-E and CFU-GEMM and the la

120 n effective vehicle for delivering the human alpha-globin gene into erythroid cells in utero, but, in

121 t the coinheritance of microdeletions in the alpha-globin gene locus in SSA patients confers "renopro

122 Applying this method to the alpha-globin gene locus in two different cell types, we

123 count; and several missense variants at the alpha-globin gene locus were associated with lower hemog

124 To investigate the role of the alpha-globin gene microdeletion and beta-globin gene clu

125 Patients with alpha-globin gene microdeletions had lower mean corpuscu

126 tors include beta-globin cluster haplotypes, alpha-globin gene number, and fetal hemoglobin expressio

127 This enhancer-independent expression of the alpha-globin gene requires extensive sequences not only

128 determine the role of these binding sites in alpha-globin gene transcription, we mutated the AP1/NFE2

129 nce of a many-body structural unit involving alpha-globin gene, its enhancers, and POL3RK gene for re

130 The residual, nonfunctional alpha-globin gene, no longer under positive selection pr

131 led that MIXL could induce expression of the alpha-globin gene, suggesting a functional conservation

132 moter directing either the EGFP or the human alpha-globin gene.

133 an gamma-globin expression/copy of the mouse alpha-globin gene.

134 d in erythroid cells expressing an exogenous alpha-globin gene.

135 udied the small second intron from the human alpha-globin gene.

136 globin genes were replaced with adult human alpha globin genes (alpha2alpha1) and a human fetal to a

137 Others, such as the alpha globin genes (HBA1 and HBA2), PDIP and BAIAP3, are

138 This 220-kb region includes the alpha globin genes and 9 widely expressed genes flanking

139 n Sri Lanka, co-inheritance of either excess alpha globin genes in beta thalassaemia heterozygotes or

140 ta heterozygotes and 8/11 (72.2%) had excess alpha globin genes.

141 a heterozygotes and 17/18 (94.4%) had excess alpha globin genes.

142 lbuminuria (13%) versus patients with intact alpha-globin genes (40%, P = 0.01).

143 of microdeletions in one or two of the four alpha-globin genes (alpha-thalassemia) was associated wi

144 ompound mutants lacking both Ahsp and 1 of 4 alpha-globin genes (genotype Ahsp(-/-)alpha-globin*(alph

145 Rattus and Peromyscus each have three adult alpha-globin genes (HBA-T1, HBA-T2 and HBA-T3), Mus has

146 e arising from the deletion of three of four alpha-globin genes (HbH) and from hemoglobin H Constant

147 Spring (HCS), caused by the deletion of two alpha-globin genes and the Constant Spring mutation.

148 hism (rSNP) in a nongenic region between the alpha-globin genes and their upstream regulatory element

149 to other globin genes, the human and rabbit alpha-globin genes are expressed in transfected erythroi

150 ctive genomic remnants of adult notothenioid alpha-globin genes but have lost the gene that encodes a

151 ts for the activation mechanism of the human alpha-globin genes by HS-40.

152 The primary goals were to assess whether the alpha-globin genes exhibit the hallmarks of spatially va

153 pression of murine embryonic zeta- and adult alpha-globin genes holds that there is a switch in globi

154 functional divergence among the triplicated alpha-globin genes in Rattus and Peromyscus, the red blo

155 e gene-dense chromatin surrounding the human alpha-globin genes is frequently decondensed, independen

156 ediated erythroid-specific activation of the alpha-globin genes is impaired solely by the insertion o

157 The alpha-globin genes provide an example of a gene family w

158 The alpha-globin genes themselves have appeared normal in al

159 e mutation, as well as microdeletions in the alpha-globin genes, could provide an epigenetic influenc

160 rs to influence the expression of the nearby alpha-globin genes, giving rise to reduced alpha-globin

161 ultilocus survey included two closely linked alpha-globin genes, HBA-T1 and HBA-T2, that underlie ada

162 one allele of chromosome 16, including both alpha-globin genes.

163 n the levels of expression of gamma, zeta or alpha-globin genes.

164 us, possesses three transcriptionally active alpha-globin genes.

165 e genotyped for beta thalassaemia mutations, alpha globin genotype and copy number and known genetic

166 The human alpha-globin (halpha-globin) gene contains 3 exons separ

167 on (3'UTR) C-rich motif of the nascent human alpha-globin (halpha-globin) transcript and enhances the

168 on of beta-globin (HBB), but not its partner alpha-globin (HBA).

169 eta-spectrin or beta-globin promoter and the alpha-globin HS40 element, a gamma-globin lentiviral vec

170 bin (cpbeta) has been coexpressed with human alpha-globin in bacterial cells and shown to associate t

171 t known how accumulation of excess unmatched alpha-globin in beta thalassemia and beta-globin in alph

172 iquitin-mediated proteolysis to degrade free alpha-globin in erythroid cells.

173 evel of approximately 0.1% that measured for alpha-globin in erythroid tissues.

174 POL3RK gene for regulating the expression of alpha-globin in silent cells.

175 a switch from the coexpression of zeta- and alpha-globin in the embryonic yolk sac to exclusive expr

176 Unbalanced production of alpha-globin in the presence of defective synthesis of b

177 s expressed at 23% +/- 16% per copy of mouse alpha-globin in transduced RBCs.

178 is distributed across both the beta- and di-alpha-globins in purified recombinant hemoglobin.

179 essed the expression of an erythroid marker, alpha-globin, indicating the ability to suppress cellula

180 ally redundant in embryos in which the adult alpha-globin is also expressed.

181 n of normal amounts of hemoglobin, even when alpha-globin is deficient, indicating unique and previou

182 AHSP also has important functions when free alpha-globin is limited.

183 gradation study showed that di-ubiquitinated alpha-globin is rapidly degraded in contrast to the mono

184 II by the heterologous introns betaIVS-I or alpha-globin IVS-II, only partially substitute (16 and 3

185 In Escherichia coli and erythroid cells, alpha globin K99E stability is rescued on coexpression w

186 When bred with human alpha globin knockin mice, homozygous CA mice survive so

187 Alpha-globin levels were not significantly changed.

188 rative sequence analysis with the functional alpha-globin loci at human Chromosome 16p13.3 and mouse

189 pha- and beta-globin genes and of homologous alpha-globin loci that occurs at nuclear speckles and co

190 gulate chromatin structure of the endogenous alpha globin locus in developing erythroblasts will prov

191 es and 9 widely expressed genes flanking the alpha globin locus.

192 deling and transcriptional activation of the alpha globin locus.

193 adjacent to the telomere, which contains the alpha-globin locus and many widely expressed genes, repl

194 The human adult alpha-globin locus consists of three pairs of homology b

195 ersensitive sites across 240 kb of the human alpha-globin locus in K562 cells.

196 ase I hypersensitive site -40 (HS-40) of the alpha-globin locus is capable of greatly enhancing expre

197 The alpha-globin locus on chromosome 16pter [lead SNP rs1333

198 homology to the pseudo-alpha2 region of the alpha-globin locus on human chromosome 16 was detected a

199 Application to alpha-globin locus shows that these constraints ( approx

200 f the LCR, and the HS-40 core element of the alpha-globin locus.

201 ccur in both duplication units of the gibbon alpha-globin locus.

202 these loci share synteny with the mammalian alpha-globin locus.

203 ences including the previously characterized alpha globin major regulatory element.

204 decreased oxidative stress and the amount of alpha-globin membrane precipitates, resulting in increas

205 aced between competing 5' splice sites in an alpha-globin minigene, direct hnRNPH/F-regulated alterna

206 re UBE2O is highly up-regulated, unassembled alpha-globin molecules that failed to assemble with beta

207 Consequently, Brg1 mutants express alpha globin mRNA at only 5-10% of wild-type levels and

208 the 3' untranslated region (3'UTR) of human alpha-globin mRNA (alpha-complex) correlates with mRNA s

209 Relative to wild-type human alpha-globin mRNA (alphawt), alphaCS mRNA is destabilize

210 High-level expression of human alpha-globin mRNA (h alpha-globin mRNA) in erythroid cel

211 reporter with UTRs from the highly expressed alpha-globin mRNA and a 72-residue poly(A) tail.

212 P complex regulates the production of mature alpha-globin mRNA by enhancing 3' processing of the halp

213 The stability of human alpha-globin mRNA correlates with assembly of a sequence

214 Robust expression of human alpha-globin mRNA during erythroid differentiation has b

215 ls treated with HMBA, including induction of alpha-globin mRNA expression, assembly of hemoglobin and

216 The alpha-globin mRNA has previously been shown to be the ta

217 ent analysis of nonsense codons in the human alpha-globin mRNA illustrates that the determinants of t

218 nclude that the alpha-complex stabilizes the alpha-globin mRNA in erythroid cells by a multifaceted a

219 ex" is essential to cytoplasmic stability of alpha-globin mRNA in erythroid cells.

220 obin gene at about 15% of the level of total alpha-globin mRNA in patients with severe beta-thalassem

221 ssion at 7% of the level of total endogenous alpha-globin mRNA in thalassemic erythroid cells resulte

222 monstrate that alpha CP is stably bound to h alpha-globin mRNA in vivo, that alpha-complex assembly o

223 Human alpha-globin mRNA is bound at a C-rich motif in the 3' u

224 Stability of the human alpha-globin mRNA is conferred by a ribonucleoprotein co

225 The stability of human alpha-globin mRNA is paralleled by formation of a sequen

226 n vivo, that alpha-complex assembly on the h alpha-globin mRNA is restricted to the 3'UTR C-rich moti

227 s reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained.

228 ma-globin expression averaged 166% of murine alpha-globin mRNA per copy in six pools and 105% in nine

229 els in MEL585 cells (averaging 75% of murine alpha-globin mRNA per copy) without reducing virus titer

230 l of Ank/(A)gamma mRNA averaged 11% of mouse alpha-globin mRNA per gene copy at all developmental sta

231 assembly extends the physical half-life of h alpha-globin mRNA selectively in erythroid cells.

232 nique contribution of the alpha-complex to h alpha-globin mRNA stability and support a model in which

233 Studies of human alpha-globin mRNA stability have identified a specific R

234 alpha-Globin mRNA stability is dictated by sequences in

235 tro studies, and the functional state of the alpha-globin mRNA targeted by alphaCP has not been defin

236 teristic organization of the poly(A) tail on alpha-globin mRNA which is maintained during normal and

237 TR alphaCP complex may serve to "prepackage" alpha-globin mRNA with its stabilizing complex prior to

238 vel expression of human alpha-globin mRNA (h alpha-globin mRNA) in erythroid cells has been specifica

239 s to enter the 3'-untranslated region of the alpha-globin mRNA, results in accelerated mRNA decay.

240 Unlike with alpha-globin mRNA, the specific cis-acting determinants

241 Unlike alpha-globin mRNA, whose stability is enhanced by assemb

242 lipoxygenase (Lox) mRNA and stabilization of alpha-globin mRNA.

243 ct from, the mechanism that stabilizes human alpha-globin mRNA.

244 t plays a critical role in stabilizing human alpha-globin mRNA.

245 n Lox mRNA and the pyrimidine-rich motifs in alpha-globin mRNA.

246 s specifically bound to actively translating alpha-globin mRNA.

247 mRNA ranging from 9% to 19% of total murine alpha-globin mRNA.

248 network is involved in stabilization of the alpha-globin mRNA.

249 ivity involved in the turnover of the stable alpha-globin mRNA.

250 ) and 8% (double copy) of the level of mouse alpha-globin mRNA.

251 id cells relative to the highly stable human alpha-globin mRNA.

252 ate the erythrocyte-specific accumulation of alpha-globin mRNA.

253 in the complex involved in stabilization of alpha-globin mRNA.

254 s challenged this view, since both zeta- and alpha-globin mRNAs can be detected simultaneously in the

255 indicate that some naturally occurring human alpha globin mutations may destabilize the protein by in

256 The alpha globin obtained from the E. coli expressed hemoglo

257 The alpha-globin of human hemoglobin was expressed in Escher

258 ucleotide polymorphism in two closely linked alpha-globin paralogs and two closely linked beta-globin

259 her amino acid differences among triplicated alpha-globin paralogs of the Norway rat (Rattus norvegic

260 on at multiple unlinked gene duplicates: two alpha-globin paralogs on chromosome 8 and two beta-globi

261 The alpha-globin poly(C) binding proteins (alphaCPs) compris

262 ated region (3'UTR) by the KH domain protein alpha-globin poly(C)-binding protein (alphaCP).

263 The alpha-globin poly(C)-binding proteins (alphaCPs) compris

264 antage over beta(S) for interaction with the alpha-globin polypeptide.

265 Sequences that contain the alpha-globin positive regulatory element (PRE) activate

266 The alpha-globin PRE contains a pair of composite binding si

267 ed that AP1/NFE2 binding sites in the murine alpha-globin PRE contribute to long-range alpha-globin g

268 iption, we mutated the AP1/NFE2 sites in the alpha-globin PRE in mice.

269 hanism that ensures proper splicing of human alpha-globin pre-messenger RNA (pre-mRNA).

270 fication loop involving oxidative stress and alpha-globin precipitation.

271 A vast excess of alpha-globin production and inadequate gamma-globin comp

272 y alpha-globin genes, giving rise to reduced alpha-globin production and to an alpha-thalassemia-like

273 recipitation that MRG15 was recruited to the alpha-globin promoter during dimethyl sulfoxide-induced

274 rise an intragenic enhancer specific for the alpha-globin promoter, but directed rearrangements of th

275 s extended to additional sites including the alpha-globin promoters.

276 of mouse Chromosome 17 including the Hba-ps4 alpha-globin pseudogene.

277 At the alpha-globin region, both the common African 3.7 kb dele

278 ated to its proximity to the remote upstream alpha-globin regulatory elements or reduced competition

279 83 and amino acids 928-960, could target the alpha-globin reporter, a cytosolic protein, to the membr

280 as identified and found to specifically bind alpha-globin, stabilize its structure, and limit the tox

281 n-S can be reversed by exchanging its normal alpha-globin subunits for zeta-globin, an endogenous, de

282 accumulation and precipitation of cytotoxic alpha-globin subunits.

283 in A assembly and protect against toxic free alpha-globin subunits.

284 each of the five regulatory elements of the alpha-globin super-enhancer individually and in informat

285 hosphorylation of eIF2alphaP, reduces excess alpha-globin synthesis and enhances translation of ATF4

286 erage gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.

287 Genetic fusion of two alpha-globins, through the introduction of a single glyc

288 zing protein (AHSP) reversibly binds nascent alpha globin to maintain its native structure and facili

289 ecombinant AHSP binds multiple forms of free alpha-globin to stabilize their structures and inhibit p

290 ighted by the inability of highly structured alpha-globins to undergo ordered oligomerization to form

291 hich ultimately leads to a rapid increase in alpha-globin transcription, occurs late in maturation.

292 t with this role, we find that alphaCP binds alpha-globin transcripts prior to splicing.

293 ich either the beta-globin Val67(E11) or the alpha-globin Val62(E11) is replaced by threonine have be

294 er define the biochemical properties of some alpha globin variants and support the hypothesis that AH

295 We analyzed 6 human alpha globin variants with altered AHSP contact surfaces

296 , in erythroid precursors, newly formed free alpha-globin was destabilized by loss of AHSP.

297 eta-thalassemic erythrocyte precursors, free alpha-globin was polyubiquitinated and degraded by the p

298 ta-globin) as well as nitrosation on Tyr-24 (alpha-globin) were identified.

299 cture, and limit the toxic effects of excess alpha-globin, which are manifest in the inherited blood

300 ule produced by the genetic fusion of two di-alpha-globins with a flexible linker demonstrated a decr