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Query: UNIPROT:P06889 (Mol)
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A novel form of regulation of expression of a vertebrate heat shock gene is described. A cDNA clone encoding human Hsp27 was shown to specifically recognize chicken Hsp23 RNA by Northern (RNA) blot analysis and hybrid-select translation. This probe was then used to measure chicken hsp23 gene activity in control and heat-stressed cells. The hsp23 gene(s) was transcriptionally active in non-heat-stressed cells, and its rate of transcription did not increase significantly upon heat shock. Cytoplasmic Hsp23 mRNA, which was metabolically very stable in nonstressed cells, underwent a fourfold increase in amount after a 1-h heat shock, resulting in a twofold increase in Hsp23 mRNA in polysomes. Hsp23 mRNA was relatively abundant and translationally active even in non-heat-shocked cells. Taken together, these data implicated posttranscriptional nuclear events as an important control point for induction of Hsp23 RNA transcripts. The protein half-life of Hsp23 increased from approximately 2 h in control cultures to 13 h in heat-shocked cells, revealing a second major control point. Hsp23 which was synthesized prior to heat shock also increased in stability and contributed to the overall accumulation of Hsp23 in heat-shocked cells. Cycloheximide had no effect on this change in Hsp23 half-life, while dactinomycin blocked the stabilization of Hsp23, suggesting a need for newly synthesized RNA. These data indicated that stabilization of Hsp23 protein and posttranscriptional nuclear events resulting in increased production of Hsp23 mRNA were primarily responsible for a 13-fold increase in the accumulation of newly synthesized Hsp23 after 1 h of heat shock. The regulation of the hsp23 gene is discussed in comparison with several other posttranscriptionally regulated genes, including the proto-oncogene c-fos, the developmentally regulated chicken delta-crystallin gene, and regulation of cellular gene expression by the proto-oncogene c-myc.
Mol Cell Biol 1990 Sep
PMID:Induction of a chicken small heat shock (stress) protein: evidence of multilevel posttranscriptional regulation. 238 29

We have determined the sequence of a rat beta A3/A1-crystallin complementary DNA (cDNA) clone and the (partial) sequence of the human beta B3-crystallin gene. Calculation of the ratio of silent to nonsynonymous substitution between orthologous beta A3/A1-, beta B3-, and other beta- and gamma-crystallin sequences revealed that the region encoding the two globular domains of the beta A3/A1-crystallin sequence is the best conserved during evolution, much better than the corresponding region of the beta B1-, beta B3-, or the gamma-crystallin sequences, and even better (at least in the rodent/frog comparison) than the well-conserved alpha A-crystallin sequence. Remarkably, the rate of change of the beta A3/A1-crystallin coding sequence does not differ in the rodent and primate lineages, in contrast with previous findings concerning the evolution rates of the alpha A- or gamma-crystallin sequences in these two lineages. Comparison of the regions that encode the four motifs of the beta-crystallin between orthologous mammalian sequences showed that the extent of nonsynonymous substitution in each of these four homologous motif regions is the same. However, when the orthologous beta-crystallin genes of more distantly related species (mammals vs chicken or frog) are compared, the extent of non-synonymous substitution is higher in the regions encoding the external motifs I and III than in the regions encoding the internal motifs II and IV. This phenomenon is also observed when paralogous members of the beta/gamma-crystallin supergene family are compared.
J Mol Evol 1989 Apr
PMID:Different evolution rates within the lens-specific beta-crystallin gene family. 249 86

gamma-Crystallins are a family of low molecular weight proteins found in high concentration in the densely packed regions of high refractive index in vertebrate lenses. Certain members have the characteristic property of a high critical temperature (tc) for phase separation. We report the three-dimensional structure determination of such a protein, bovine lens gamma IVa-crystallin, which has been refined to give an X-ray R-factor of 0.143. Its high tc contrasts with the low tc gamma II-crystallin, whose structure we have already published. The root mean square difference between the alpha-carbon atoms of these two proteins is 0.70 A and gamma IVa has an internal symmetry even higher than that of gamma II. The presence of a protein that exhibits the phenomenon of phase separation at body temperature renders the lens very susceptible to a transformation from transparent to an opaque state due to irregularities in the refractive index. Protein interactions of gamma IVa-crystallin have implications for the mechanism of cataract formation. Modes of self-association behaviour of gamma IVa-crystallin have been inferred from an analysis of the lattice interactions in the crystalline state, where the protein packing density is similar to that of the intact lens. It appears that the point mutation at position 103 from a serine residue in gamma II to a valine in gamma IVa gives rise to a lattice contact formed by two four-stranded beta-sheets in gamma IVa. A group-specific mutation at position 118 from leucine to phenylalanine induces subtle differences in core packing, leading to a reorganization around residue 103. However, the final phase separation determinant may be a complex combination of many side-chain functions.
J Mol Biol 1989 May 05
PMID:Packing interactions in the eye-lens. Structural analysis, internal symmetry and lattice interactions of bovine gamma IVa-crystallin. 273 25

Sequences in the two delta-crystallin genes become hypomethylated when they are expressed in the chick lens. This system is particularly advantageous for studying temporal changes in hypomethylation, since lens tissue can be isolated at all developmental stages. In previous work we have shown that most HpaII sites become hypomethylated within the delta 1-crystallin gene long after delta-crystallin gene activation. One site is hypomethylated when crystallin mRNA begins to be synthesized at high levels at 50 h; we show here that this site maps to the 3' end (intron 15) of the delta 1-crystallin gene. In addition, we have examined the methylation status of HpaII and HhaI sites found near the 5' end of the delta 1-crystallin gene. Two HhaI sites adjacent to a viral core enhancer sequence in intron 2 are also first hypomethylated at 50 h. These findings point to regions of the delta 1 gene that should be investigated further for functional significance in regulating delta-crystallin transcription.
Mol Cell Biol 1989 Jul
PMID:Developmental regulation of hypomethylation of delta-crystallin genes in chicken embryo lens cells. 277 57

A cloned chicken delta-crystallin cDNA was used to identify two putative delta-crystallin genes in the duck by Southern blot hybridization. A DNA fragment containing most of one of these genes was isolated from a library made in bacteriophage lambda Charon 28A containing genomic DNA from 14-day-old embryonic ducks. Electron microscopy, partial gene sequencing, primer extension analysis using duck mRNA, and comparison with the well-characterized chicken delta-crystallin genes suggest that our cloned duck delta-crystallin gene, like the chicken delta-crystallin genes, is 8-10 kb long and contains 17 exons. Hybridization and sequencing data show great similarity between the homologous 5' untranslated and coding exons of the duck and chicken delta-crystallin genes. Overall, the homologous introns also appear to have approximately 30% sequence similarity, and have been subject to deletion/insertion events. Our partial characterization of duck delta-crystallin gene sequences suggests that this avian and reptilian crystallin family has been conserved during evolution, as have the other crystallin gene families that are expressed in the eye lens.
J Mol Evol 1987
PMID:Conservation of delta-crystallin gene structure between ducks and chickens. 282 41

A culture system was developed which permitted the differentiation of chicken lens epithelial cells to lentoid bodies which contained several cell layers, accumulated high levels of delta-crystallin, and produced extensive gap junctions. This differentiation process was prevented when the cells were infected with a temperature-sensitive src mutant of Rous sarcoma virus and maintained at the permissive temperature. These transformed cells continued to proliferate and also synthesized the major lens gap junction protein, MP28, at near-normal rates. However, this MP28 was not assembled to produce gap junctions. Cultures shifted to the nonpermissive temperature formed lentoid bodies similar to those in uninfected lens cultures, including the establishment of gap junctions containing MP28.
Mol Cell Biol 1988 Apr
PMID:Inhibition of chicken embryo lens differentiation and lens junction formation in culture by pp60v-src. 283 40

Short range, liquid-like order of the crystallin proteins accounts for eye lens transparency. The relationship between structural and thermodynamic properties of eye lens was further investigated using osmotic pressure and small-angle X-ray scattering measurements of calf lens alpha-crystallins. The consistency of both data sets confirms that the macroscopic thermodynamic properties are determined by the structural properties accessible to X-ray scattering. In addition, the experimental data were correctly accounted for using a model developed in liquid-state physics: the rescaled mean spherical approximation combined with a Verwey-Overbeek potential. This model provides as best fit parameters the excluded volume, the charge and the diameter of an "equivalent" particle that compare well with the corresponding values found in the literature for alpha-crystallins. As a result, transparency may now be expressed as a function of a few structural parameters, the role of which is discussed. The approach presented here may be extended to studies of the thermodynamic-structural relationships of other protein solutions.
J Mol Biol 1989 Feb 20
PMID:Molecular basis of eye lens transparency. Osmotic pressure and X-ray analysis of alpha-crystallin solutions. 292 23

Rat genomic clones, which together contain all of the rat genomic gamma-crystallin sequences, have been characterized. Five gamma-crystallin genes are located on a contiguous DNA region, 63 X 10(3) base-pairs long. These genes, named (5') gamma 1-1, gamma 1-2, gamma 2-2 and gamma 3-1 (3'), are all oriented head to tail. A sixth gamma-crystallin gene, named the gamma 4-1 gene, could not be linked to the gamma-crystallin gene cluster with our present set of genomic clones. Mapping experiments using single copy sequences which form the extreme 5' or 3' region of the gene cluster showed that, if the gamma 4-1 gene is located on the same chromosome, then it must be separated from the gene cluster by at least 25 X 10(3) base-pairs of DNA. All gamma-crystallin genes have a similar mosaic structure. They contain a large (0.9 X 10(3) to 1.88 X 10(3) base-pairs) intron in the middle of the gene and are further interrupted close to the 5' end of the gene. The length of the first exon varies from about 40 to about 50 base-pairs. The complementary DNA clone pRL-gamma-3 used in this study is a copy of the transcript of the gamma 3-1 gene, while the second complementary DNA clone, pRL-gamma-2, is most likely a copy of the transcript of the gamma 2-1 gene. It is further shown that rat lens messenger RNA protects fragments from the 3' ends of the four other gamma-crystallin genes against degradation by S1 nuclease, hence all six gamma-crystallin genes present in the rat genome must be transcribed in the lens. Repetitive sequences were found to be present between and around the gamma-crystallin genes. Mapping with cloned repetitive sequences showed that three different repeats, designated A, B and C, occur more than once in the gamma-crystallin gene cluster. Repeat C is also found in the gamma 4-1 region. A repetitive region 3' to the gamma 3-1 gene contains members of all three repeat families.
J Mol Biol 1985 Apr 05
PMID:Characterization of the rat gamma-crystallin gene family and its expression in the eye lens. 298 30

The multigene family for human gamma-crystallin has been assigned to chromosome 2 using rodent-human somatic cell hybrids and filter hybridization analysis of cell hybrid DNA. Two genomic DNA probes containing human gamma-crystallin gene sequences hybridize to five fragments in human DNA digested with the restriction enzyme EcoRI. By correlating the presence of these fragments in somatic cell hybrid DNA with the human chromosome content of the hybrids, at least six human gamma-crystallin genes can be mapped to chromosome 2. Data obtained with a hybrid clone containing a mouse-human interspecies translocation suggest that these genes may be clustered together on the long arm of human chromosome 2.
Somat Cell Mol Genet 1985 Sep
PMID:Assignment of human gamma crystallin multigene family to chromosome 2. 299 42

alpha A-Crystallin, a major structural polypeptide of the vertebrate eye lens, is evolutionarily highly conserved. We have analyzed the corresponding nucleic acid sequences in both genomic DNA digests as well as in lens cytoplasmic RNA preparations from a wide variety of vertebrates by blot hybridization with cloned rat alpha A2-crystallin cDNA probes. The probes are not able to hybridize under any conditions to RNA and DNA derived from fishes and amphibia, but do show substantial homology with the sequences of mammals, birds and reptiles. The alpha A-crystallin gene, which has been isolated from a hamster gene library occurs only once in the haploid genome. Coding and 3'-untranslated regions of alpha A2-crystallin mRNA are conserved among all mammals and birds examined. However, the regions comprising the conserved sequences are differently represented in the ultimate mRNA. The alpha A2-mRNA 3'-non-coding regions of reptiles and birds are 300-550 bases longer than those of mammals. Some rodents produce next to the alpha A2-mRNA another messenger that encodes the alpha AIns-polypeptide possessing an insertion of 22/23 amino acid residues between positions 63 and 64 of the alpha A2-polypeptide chain. alpha A2 and alpha AIns-mRNA are generated from a single gene as major and minor species, respectively, in a proportion which is similar to the ratio of the polypeptides found in vivo and in vitro. The size heterogeneity of the alpha A2-mRNA from most mammals examined is due to the variable size of the poly(A) tail.
Mol Biol Rep 1985 Oct
PMID:Evolution of the single copy alpha A-crystallin gene: differently sized mRNAs of mammals and birds show homology in their 3' non-coding regions. 299 79


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