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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crystallins, the major gene products of the lens, accumulate to high levels during the differentiation of the vertebrate lens. Although crystallins were traditionally thought to be lens specific, it has recently been shown that some are also expressed at very low levels in nonlens tissues. We have examined the embryonic expression pattern of gamma-crystallins, the most abundant crystallins of the embryonic lens in Xenopus laevis. The expression profile of five Xenopus gamma-crystallin genes mirrors the pattern of lens differentiation in X. laevis, exhibiting on average a 100-fold increase between tailbud and tadpole stages. Four of these genes are also ubiquitously expressed outside the lens at a very low level, the first demonstration of nonlens expression of any gamma-crystallin gene; expression of the remaining gene was not detected outside the head region, thus suggesting that there may be two classes of gamma-crystallin genes in X. laevis. Predictions regarding control mechanisms responsible for this dual mode of expression are discussed. This study raises the question of whether any crystallin, on stringent examination, will be found exclusively in the lens.
Mol Cell Biol 1994 Feb
PMID:Xenopus gamma-crystallin gene expression: evidence that the gamma-crystallin gene family is transcribed in lens and nonlens tissues. 750 4

The in vitro effect of glucose on cultured rat lenses was correlated with (i) the time-dependent leakage of lactate dehydrogenase (LDH) into defined medium; (ii) the appearance of the lens under the dissection microscope; and (iii) the leakage of lens cytosolic proteins. A protective effect of 1 mM Vitamin C (VC) was also found: the extent of opacification, LDH and gamma-crystallin release were reduced if 1 mM VC was included in the medium. Using the above parameters provides a new and more rapid technique to follow lens opacification in vitro.
Biochem Mol Biol Int 1995 Apr
PMID:Modelling cortical cataractogenesis. 16. Leakage of lactate dehydrogenase: a new method for following cataract development in cultured lenses. 754 33

The effect of streptozocin diabetes of 14 days duration on the integrity of lenticular crystallins has been determined by the measurement of characteristic markers of protein modification in the lens crystallins of rats. Further, the susceptibility of the crystallins to modification has also been determined by measurement of the same markers after the application of a metal-catalyzed oxidative insult in vitro. The results show that the previously reported increased post-translational modification of lens crystallins in vivo and increased susceptibility to modification in vitro of diabetic crystallins after 21 days of uncontrolled diabetes are also evident after just 14 days of diabetes. Treatment of the diabetic animals with the antioxidant ubiquinone by dietary supplementation was unable to prevent the post-translational modifications sustained by the crystallin when subjected to diabetes in vivo or the increase in susceptibility to an in vitro oxidative stress. While the present results support the proposal that cataract formation is initiated by protein post-translational modification factors such as glycation, ubiquinone supplementation does not appear to be beneficial in the inhibition of post-translational crystallin modification in diabetic cataractogenesis.
Biochem Mol Med 1995 Aug
PMID:Effect of diabetes and dietary ubiquinone supplementation on the post-translational modification of rat lens beta L crystallin. 758 76

gamma-Crystallin is the major and most abundant lens protein present in the eye lens of most teleostean fishes. To facilitate structural characterization of gamma-crystallins isolated from the lens of the catfishes (Clarias fuscus), a cDNA mixture was synthesized from the poly(A)+mRNA isolated from fresh eye lenses, and amplification by polymerase chain reaction (PCR) was adopted to obtain cDNAs encoding various gamma-crystallins. Plasmids of transformed E. coli strain JM109 containing amplified gamma-crystallin cDNAs were purified and prepared for nucleotide sequencing by the dideoxynucleotide chain-termination method. Sequencing more than five clones containing DNA inserts of 0.52 kb revealed the presence of one major isoform with a complete reading frame of 534 base pairs, covering a gamma-crystallin (gamma M1) with a deduced protein sequence of 177 amino acids excluding the initiating methionine. It was of interest to find that this crystallin of pI 9.1 contains a high-methionine content of 15.3% in contrast to those gamma-crystallins of low-methionine content from most mammalian lenses. Sequence comparisons of catfish gamma M1-crystallin with those published sequences of gamma-crystallins from carp, bovine and mouse lenses indicate that there is approx. an 82% sequence homology between the catfish and the carp species of piscine class whereas only 51-58% homology is found between mammals and the catfish. Moreover the differences in the hydropathy profiles for these two groups of gamma-crystallins, i.e. one with a high-methionine content from teleostean fishes and the other with a low-methionine content from mammalian species, reflect a distinct variance in the polarity distributions of surface amino acids in these crystallins.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochem Mol Biol Int 1995 Apr
PMID:Characterization of gamma-crystallin from a catfish: structural characterization of one major isoform with high methionine by cDNA sequencing. 762 23

omega-Crystallin of the octopus lens is related to aldehyde dehydrogenases (ALDH) of vertebrates (Tomarev, S. I., Zinovieva, R. D., and Piatigorsky, J. (1991) J. Biol. Chem. 266, 24226-24231) and ALDH1/eta-crystallin of elephant shrews (Wistow, G., and Kim, H. (1991) J. Mol. Evol. 32, 262-269). Only very low amounts of omega-crystallin are present in the squid lens. Here, we have cloned omega-crystallin cDNAs of the octopus (Octopus dofleini) and squid (Ommastrephes sloani pacificus) lenses. The deduced amino acid sequences of omega-crystallin from these species are 78% identical to each other, 56-58% identical to cytoplasmic ALDH1 and mitochondrial ALDH2 of vertebrates (which are 66-68% identical to each other), and 40% identical to Escherichia coli and spinach ALDHs. These data are consistent with the idea that the ALDH1/ALDH2 gene duplication in vertebrates occurred after divergence of cephalopods from the line giving rise to vertebrates, but before the separation of squid and octopus. Southern blot hybridization indicated that omega-crystallin is encoded by few genes (possibly just one) in octopus and squid. Northern blot hybridization revealed two bands (2.7 and 9.0 kilobases) of omega-crystallin RNA in the octopus lens and one band (4.2 kilobases) in the squid lens; omega-crystallin RNAs were undetectable in numerous non-lens tissues of octopus and squid, suggesting lens-specific expression of this gene(s). Finally, extracts of the octopus lens had no detectable ALDH activity using different substrates, consistent with omega-crystallin having no enzymatic activity. Taken together, our results suggest that omega-crystallin evolved by duplication of an ancestral gene encoding ALDH and subsequently specialized for refraction in the transparent lens while losing ALDH activity and expression in other tissues.
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PMID:Aldehyde dehydrogenase-derived omega-crystallins of squid and octopus. Specialization for lens expression. 768 83

Crystallins are proteins that accumulate to very high concentrations in the fiber cells of the lens of the eye. Crystallins are responsible for the transparency and high refractive index that are essential for lens function. In the chicken embryo, delta-crystallin accounts for more than 70% of the newly synthesized lens proteins. We used density labeling and gene-specific polymerase chain reaction (PCR) to determine the mechanism regulating the expression of the two very similar delta-crystallin genes. Newly synthesized RNA was separated from preexisting RNA by incubating the lenses with 15N- and 13C-labeled ribonucleosides and then separating newly synthesized, density-labeled RNA from the bulk of light RNA by equilibrium density centrifugation in NaI-KI gradients. The relative abundances of the two crystallin mRNAs in the separated fractions were then determined by PCR. This method permitted the quantitation of newly synthesized processed and unprocessed delta-crystallin mRNAs. Additional studies used intron- and gene-specific PCR primers to determine the relative expression of the two delta-crystallin genes in processed RNA and unprocessed RNA extracted from different regions of the embryonic lens. Results of these tests indicated that the differential expression of the delta-crystallin genes was regulated primarily at the level of transcription. This outcome was not expected on the basis of the results of previous studies, which used in vitro transcription and transfection methods to evaluate the relative strengths of delta-crystallin promoter and enhancer sequences. Our data suggest that the cultured cells used in these earlier studies may not have provided an accurate view of delta-crystallin regulation in the intact lens.
Mol Cell Biol 1993 Jun
PMID:Transcriptional control of delta-crystallin gene expression in the chicken embryo lens: demonstration by a new method for measuring mRNA metabolism. 768 94

The ever-increasing number of proteins identified as belonging to the family of small heat-shock proteins (shsps) and alpha-crystallins enables us to reassess the phylogeny of this ubiquitous protein family. While the prokaryotic and fungal representatives are not properly resolved, most of the plant and animal shsps and related proteins are clearly grouped in distinct clades, reflecting a history of repeated gene duplications. The members of the shsp family are characterized by the presence of a conserved homologous "alpha-crystallin domain," which sometimes is present in duplicate. Predictions are made of secondary structure and solvent accessibility of this domain, which together with hydropathy profiles and intron positions support the presence of two similar hydrophobic beta-sheet-rich motifs, connected by a hydrophilic alpha-helical region. Together with an overview of the newly characterized members of the shsp family, these data help to define this family as being involved as stable structural proteins and as molecular chaperones during normal development and induced under pathological and stressful conditions.
J Mol Evol 1995 Mar
PMID:The expanding small heat-shock protein family, and structure predictions of the conserved "alpha-crystallin domain". 772 51

Two cis-acting promoter elements (-108 to -100 and -49 to -33) of the mouse alpha A-crystallin gene, which is highly expressed in the ocular lens, were studied. Here we show that DE1 (-108 to -100; 5'TGACGGTG3'), which resembles the consensus cyclic AMP (cAMP)-responsive element sequence (CRE; 5'TGACGT[A/C][A/G]3'), behaves like a functional CRE site. Transfection experiments and electrophoretic mobility shift assays (EMSAs) using site-specific mutations correlated a loss of function with deviations from the CRE consensus sequence. Results of EMSAs in the presence of antisera against CREB, delta CREB, and CREM were consistent with the binding of CREB-like proteins to the DE1 sequence. Stimulation of alpha A-crystallin promoter activity via 8-bromo-cAMP, forskolin, or human T-cell leukemia virus type I Tax1 in transfections and reduction of activity of this site in cell-free transcription tests by competition with the somatostatin CRE supported the idea that DE1 is a functional CRE. Finally, Pax-6, a member of the paired-box family of transcription factors, activated the mouse alpha A-crystallin promoter in cotransfected COP-8 fibroblasts and bound to the -59 to -29 promoter sequence in EMSAs. These data provide evidence for a synergistic role of Pax-6 and CREB-like proteins for high expression of the mouse alpha A-crystallin gene in the lens.
Mol Cell Biol 1995 Feb
PMID:Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site. 782 34

Previously, we have identified a hormone response element (gamma F-HRE) composed of an everted repeat of the half-site (A/G)GGTCA motif separated by 8 base pairs that mediates retinoic acid (RA) activation of the gamma F-crystallin promoter. Here, we report that this element is bound by the thyroid hormone (T3) receptor in the form of heterodimers with either the retinoid X receptor (RXR) or the retinoic acid receptor (RAR). The T3R/RXR heterodimer binds to this element with high affinity but the transcriptional activity of the T3 receptor on this element is effectively antagonized by RAR alpha. Thus, RAR alpha exerts a dominant effect on the gamma F-HRE-everted repeat by mediating both RA activation and preventing T3 response. Although RAR/T3R heterodimers bind to the gamma F-HRE, they do not appear to be involved in transcriptional regulation since they bind with low affinity, and their ability to bind DNA is dramatically decreased by T3. Repression requires the DNA- and ligand-binding domains of RAR alpha and is consistent with a competitive DNA binding model of repression. However, in vitro binding studies indicate that RAR/RXR heterodimers form less stable interactions with the gamma F-HRE compared with T3R/RXR heterodimers; this suggests that in vivo the binding affinity of RAR/RXR heterodimers may be enhanced by accessory factors.
Mol Endocrinol 1994 Nov
PMID:Heterodimeric interaction of the retinoic acid and thyroid hormone receptors in transcriptional regulation on the gamma F-crystallin everted retinoic acid response element. 787 18

The complete sequence was determined for the chicken beta B1-crystallin gene and 2.2 kbp of its 5' flanking region; the chicken gene was then compared to its rat ortholog. Although both have a 5' non-coding exon followed by 5 protein coding exons, the chicken gene is only 2.2 kbp while the rat gene is 13.6 kpb due to longer introns. The coding exons of the chicken beta B1-crystallin gene, like those of the rat and other beta-crystallin genes, each correspond to one of the four 'Greek key' motifs of the encoded protein. The only obvious similarity between the 5' flanking sequences of the chicken and rat beta B1-crystallin gene is associated with the TATA box. A CR1 repetitive element is present at positions -559 to -730 of the chicken beta B1-crystallin gene. In vivo footprinting using dimethyl sulfate/ligation mediated PCR showed that the PL-1 (-116/-102), PL-2 (-90/-76), OL-2 (-75/-68) and OL-1 (-125/-118) control elements identified previously (Roth et al. (1991) Mol. Cell. Biol. 11, 1488-1499) bind proteins within the chromatin of cultured embryonic chicken lens cells. Both -2448/+30 and -434/+30 promoter fragments from the chicken beta B1-crystallin gene directed lens-specific CAT gene expression in a copy number and position independent manner in transgenic mice. These data indicate that the structure and lens-specific expression of this gene are highly conserved although, like other crystallin genes, the 5' flanking sequences have diverged appreciably during evolution.
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PMID:Chicken beta B1 crystallin: gene sequence and evidence for functional conservation of promoter activity between chicken and mouse. 789 62


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