The structure, expression, function and evolution of the crystallin genes of vertebrates and invertebrates are being studied. The autophosphorylation of alphaA- but not alphaB-crystallin was shown to be enhanced by tetramerization, and alphaB was shown to be a better substrate than alphaA for cAMP-dependent phosphorylation. Further studies were directed to testing the idea that Pax- 6 is a universal activator of crystallin genes. Pax-6 was shown to activate the alphaB--crystallin was shown to be enhanced by tetramerization, and alphaB was shown to be a better substrate than alpha for cAMP-dependent phosphorylation. Further studies were directed to testing the idea that Pax-6 is a universal activator of crystallin genes. Pax-6 was shown to activate the alphaB- and bind the betaB2-crystallin mouse promoters; earlier studies have linked Pax-6 to expression of the mouse and chicken alphaA- , chicken delta1-, and guinea pig zeta-crystallin promoters. A Pax-6 cDNA was cloned from squid, and a partial Pax gene and cDNA were cloned from jellyfish. Another lens transcription factor, Prox-1, was cloned from chicken and mouse and shown to be expressed early in the developing lens placode of chickens. Both Pax-6 and Prox-1 mRNAs are alternatively spliced in tissue-preferred fashions. Evidence was obtained that the transcription factors HSF1 and/or HSF2 may activate expression of the nonstress inducible alphaA- and gammaF-crystallin genes. A complex developmental pattern was shown for mouse alphaB- crystallin promoter activity in transgenic mice, and cis- control elements were identified or studied further for the mouse alphaA-(PE1 and PE2) and alphaB- (alphaBE-4, LSR, LSE) and chicken betaB1- (PL1, PL2, -126/53 region) and betaA3/A1-(-96/-60 region) genes. Transgenic mice established that the chicken delta1- and delta2-crystallin enhancers work equally well in the lenses of transgenic mice; thus, the low endogenous expression of delta2 gene in the chicken lens remains unexplained. New lens cell lines synthesizing alpha-crystallins were obtained, and a number of crystallin cDNAs and genes (chicken betaA2, betaA4, and betaB3; jellyfish J3: squid S) were cloned and in some cases chromosomally mapped and cellularly localized. Squid glutathione S-transferase (GST) has been placed in a new group (s) after solving its x-ray structure. Only one S- crystallin (SL11/Lops4, lacking a central insert) was shown to have GST activity, leading to a model for S-crystallin evolution from GST. Glutamate decarboxylase was shown to be transiently expressed in the embryonic rat lens central fiber cells during nuclear breakdown. Finally, evidence was obtained that expression of Alzheimer's beta-amyloid precursor protein and beta-amyloid peptide is stimulated in lens by oxidative stress and may contribute to cataract.
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