Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1384489 (Scratch)
 395 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the Snail family of zinc finger transcription factors are known to play critical roles in neurogenesis in invertebrates, but none of these factors has been linked to vertebrate neuronal differentiation. We report the isolation of a gene encoding a mammalian Snail family member that is restricted to the nervous system. Human and murine Scratch (Scrt) share 81% and 69% identity to Drosophila Scrt and the Caenorhabditis elegans neuronal antiapoptotic protein, CES-1, respectively, across the five zinc finger domain. Expression of mammalian Scrt is predominantly confined to the brain and spinal cord, appearing in newly differentiating, postmitotic neurons and persisting into postnatal life. Additional expression is seen in the retina and, significantly, in neuroendocrine (NE) cells of the lung. In a parallel fashion, we detect hScrt expression in lung cancers with NE features, especially small cell lung cancer. hScrt shares the capacity of other Snail family members to bind to E-box enhancer motifs, which are targets of basic helix--loop--helix (bHLH) transcription factors. We show that hScrt directly antagonizes the function of heterodimers of the proneural bHLH protein achaete-scute homolog-1 and E12, leading to active transcriptional repression at E-box motifs. Thus, Scrt has the potential to function in newly differentiating, postmitotic neurons and in cancers with NE features by modulating the action of bHLH transcription factors critical for neuronal differentiation.
 ...
PMID:Mammalian Scratch: a neural-specific Snail family transcriptional repressor. 1127 25

The C2H2 zinc finger is one of the most common domains encoded by animal genomes and has been implicated in DNA binding as well as protein-protein interactions and RNA binding. Genes encoding C2H2 zinc finger domains include not only well-studied conserved transcription factors such as Gli and Snail but also include a large diversity of more rapidly evolving genes. Here, I focus on the description of amphioxus members of families and super-families of C2H2 zinc finger genes that have been the subject of functional studies in other species, specifically the Gli, Zic, Glis, Snail, Scratch, Krox, Wilms' tumour, Huckebein, SP, KLF, Ovo, Spalt, Blimp-1, Odd and Fez genes. Surveys of the Branchiostoma floridae genome reveal members of all of these groups of genes. Genes are named according to molecular phylogenetic analyses, such that the nomenclature reflects pre-existing gene names in the context of gene families that have descended from a single common ancestral gene in the common ancestor of chordates and insects. In total, this comprises 28 B. floridae C2H2 zinc finger genes, representing at least 15 gene families. For 17 of these genes, expressed sequence tag clusters and associated clone identification codes relating to the B. floridae gene collection are given.
 ...
PMID:C2H2 zinc finger genes of the Gli, Zic, KLF, SP, Wilms' tumour, Huckebein, Snail, Ovo, Spalt, Odd, Blimp-1, Fez and related gene families from Branchiostoma floridae. 1879 22

Scratch (scrt) genes are neural-specific in mammals, but their homologues have not been well studied in non-mammalian vertebrates. In this report, we isolated three zebrafish scrt genes, scratch1a (scrt1a), scratch1b (scrt1b), and scratch2 (scrt2), which belong to the Snail superfamily of zinc finger transcription factors. Spatiotemporal expression analysis revealed that scrt1a and scrt2 were initially detected in the central nervous system (CNS) during early somitogenesis while scrt1b was first detectable in neuronal clusters in the brain during late somitogenesis. Interestingly, scrt-expressing cells largely overlapped with huC-positive differentiating neurons and partially with neurogenin1-positive neuronal precursor cells. In addition, scrt-expressing cells were dramatically increased in mind bomb, a neurogenic mutant. Taken together, these results suggest that each zebrafish scrt gene is specifically expressed in neuronal cells and may be involved in differentiation of distinct neuronal populations in the vertebrate nervous system.
 ...
PMID:Neuron-specific expression of scratch genes during early zebrafish development. 2144 84

Members of the Snail/Gfi-1 domain family of zinc finger proteins are known to recognize the E-box sequence CANNTG, such as that found in the promoter of E-cadherin, however, no studies have shown that the internal "NN" dinucleotides can play a role in different binding affinities. We show via gel shift assays that only the sequences CACCTG and CAGGTG can be recognized more strongly by the SNAG-ZFP members such as Slug, Smuc, Snail, and Scratch while the other combinations of the internal nucleotides were bound weakly. All 16 possible dinucleotide combinations were tested by competition EMSAs to determine their relative binding affinities. The Kd value for the best-binding sequences was approximately 1.25 x 10(-6) M, while the other interactions were less effective. Our study has shown for the first time how different internal dinucleotide combinations of the E-box can be recognized differently by different transcription factors and also sheds light into how this transcription factor binding site may participate in DNA-protein interactions.
 ...
PMID:Characterization of the E-box binding affinity to snag-zinc finger proteins. 2335 Feb 37