Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous genetic studies, this molecular similarity supports the suggestion of a common mechanism used for generating heterochromatin and for repressing homeotic genes. The evolutionary conservation of the chromo domain throughout the animal and plant kingdoms implies an important functional role for this protein motif. We have used transgenic lines as well as transient expression assays employing Drosophila tissue culture cells to study the functional role of the Pc chromo domain. Wild-type Pc protein is endogenously expressed in SL2 cells and is found in large immunologically visible complexes. Mutated Pc proteins were expressed as Pc-beta-galactosidase fusion proteins, and their nuclear distribution was examined by indirect immunofluorescence in tissue culture cells and on polytene chromosomes of transgenic larvae. We show that carboxy-terminal truncations of the Pc protein do not affect chromosomal binding of the fusion protein. However, mutations affecting only the chromo domain including in vitro generated deletions, as well as point mutations, abolish chromosomal binding. Our results demonstrate for the first time that the chromo domain is important for the function of Pc and that it is absolutely required for binding of Pc protein to chromatin. Some of the nuclear patterns generated by the mutated forms of the fusion proteins suggest, furthermore, that the chromo domain could be involved in a packaging mechanism, essential for compacting chromosomal proteins within heterochromatin or heterochromatin-like complexes.
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PMID:Analysis of the functional role of the Polycomb chromo domain in Drosophila melanogaster. 162 30

The Drosophila protein HP1 is a 206 amino acid heterochromatin-associated nonhistone chromosomal protein. Based on the characterization of HP1 to date, there are three properties intrinsic to HP1: nuclear localization, heterochromatin binding, and gene silencing. In this work, we have concentrated on the identification of domains responsible for the nuclear localization and heterochromatin binding properties of HP1. We have expressed a series of beta-galactosidase/HP1 fusion proteins in Drosophila embryos and polytene tissue and have used beta-galactosidase enzymatic activity to identify the subcellular localization of each fusion protein. We have identified two functional domains in HP1: a nuclear localization domain of amino acids 152-206 and a heterochromatin binding domain of amino acids 95-206. Both of these functional domains overlap an evolutionarily conserved COOH-terminal region.
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PMID:Overlapping domains of the heterochromatin-associated protein HP1 mediate nuclear localization and heterochromatin binding. 842 Oct 49

The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) inhibits hematopoietic stem cell (HSC) expansion, interferes with HSC self-renewal and compromises the ability of HSC to reconstitute hematopoiesis. We have investigated mechanisms by which TNFalpha suppresses hematopoiesis using the genomic instability syndrome Fanconi anemia mouse model deficient for the complementation-group-C gene (Fancc). Examination of senescence makers, such as senescence-associated beta-galactosidase, HP1-gamma, p53 and p16(INK4A) shows that TNFalpha induces premature senescence in bone marrow HSCs and progenitor cells as well as other tissues of Fancc-/- mice. TNFalpha-induced senescence correlates with the accumulation of reactive oxygen species (ROS) and oxidative DNA damage. Neutralization of TNFalpha or deletion of the TNF receptor in Fancc-/- mice (Fancc-/-;Tnfr1-/-) prevents excessive ROS production and hematopoietic senescence. Pretreatment of TNFalpha-injected Fancc-/- mice with a ROS scavenger significantly reduces oxidative base damage, DNA strand breaks and senescence. Furthermore, HSCs and progenitor cells from TNFalpha-treated Fancc-/- mice show increased chromosomal aberrations and have an impaired oxidative DNA-damage repair. These results indicate an intimate link between inflammatory reactive oxygen species and DNA-damage-induced premature senescence in HSCs and progenitor cells, which may play an important role in aging and anemia.
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PMID:Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence. 1740 15