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

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

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

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

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

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

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

15 Here we map a limited segment of the alpha-globin 3'UTR that is both necessary and sufficient

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 ute need for zeta-globin and indicating that alpha-globin alone can serve the survival needs of the f

27 1 of 4 alpha-globin genes (genotype Ahsp(-/-)alpha-globin*(alpha/alphaalpha)) exhibited more severe a

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

29 Alpha globin amino acid substitutions H103Y, H103R, F117

30 5% for 3H-alpha-chains and 47% to 96% for 3H-alpha-globin among the four hemolysates.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

56 ains, leading to the precipitation of excess alpha-globin chains to form Heinz bodies.

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

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

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

60 is category, contained not only precipitated alpha-globin chains, but also beta chains.

61 parently due to the imbalance of beta-versus alpha-globin chains, leading to the precipitation of exc

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

86 Alpha globin expression must be regulated properly to pr

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

180 Alpha-globin levels were not significantly changed.

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

182 tivate expression of the endogenous beta- or alpha-globin loci in this cell line.

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

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

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

186 deling and transcriptional activation of the alpha globin locus.

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

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

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

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

191 he sequence organization of the entire adult alpha-globin locus of gibbon (Hylobates lar).

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

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

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

195 is the major regulatory element of the human alpha-globin locus, located 40 kb upstream of the zeta-g

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

218 The ratio of adult beta-globin/alpha-globin mRNA in the mutant ES cells was 1/15 of tha

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

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

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

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

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

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

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

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

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

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

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

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

231 alpha-Globin mRNA stability is dictated by sequences in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

270 Furthermore, the alpha-globin promoter is more active in the context of a

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

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

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

274 on to incorporation into a HbA tetramer, the alpha-globin refolds and incorporates heme in the absenc

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

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

277 83 and amino acids 928-960, could target the alpha-globin reporter, a cytosolic protein, to the membr

278 bA2), which contains delta-globin as its non-alpha-globin, represents a minor fraction of the Hb foun

279 rom the factors necessary for binding to the alpha-globin sequence.

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