Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CCR4 gene from Saccharomyces cerevisiae is required for the transcription of the glucose-repressible alcohol dehydrogenase (ADH2). Mutations in CCR4 also suppress the transcription at the ADH2 and his4-912delta loci caused by defects in the SPT10 (CRE1) and SPT6 (CRE2) genes. The CCR4 gene was mapped to the left arm of chromosome I and cloned by complementation of function using previously isolated segments of chromosome I. DNA sequence analysis of the cloned gene defined CCR4 as a 2511 bp open reading frame that would encode a polypeptide of 837 amino acids. The CCR4 mRNA was found to be 2.8 kb in size and Western analysis identified CCR4 as a 95,000 D protein. Disruption of the CCR4 gene resulted in reduced levels of ADH2 expression under both glucose and ethanol growth conditions and in temperature sensitive growth on nonfermentative medium, phenotypes essentially indistinguishable from previously identified mutations in CCR4. The amino terminus of the CCR4 protein was found to be rich in glutamine residues similar to a number of genes which are required for transcription. More importantly, CCR4 showed similarity to a diverse set of proteins sharing a leucine-rich tandem repeat motif, the presence of which has been implicated in mediating protein-protein interactions. Deletions of several of the five leucine-rich repeats in CCR4 were shown to produce nonfunctional proteins indicating the importance of the repeats to CCR4 activity. This leucine-rich repeat region may mediate the contact CCR4 makes with another factor.
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PMID:The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression. 145 46

Mutations in the yeast CCR4 gene inhibit expression of the glucose-repressible alcohol dehydrogenase (ADH2), as well as other nonfermentative genes, and suppress increased ADH2 expression caused by the cre1 and cre2 alleles. Both the cre1 and ccr4 alleles were shown to affect ADH II enzyme activity by altering the levels of ADH2 mRNA. Mutations in either CRE1 or CRE2 bypassed the inhibition of ADH2 expression caused by delta insertions at the ADH2 promoter which displace the ADH2 activation sequences 336 bp upstream of the TATA element. These cre1 and cre2 effects were suppressible by the ccr4 allele. The cre1 and ccr4 mutations also affected ADH2 expression when all the ADH2 regulatory sequences upstream of the TATA element were deleted. The relationship of the CRE genes to the SPT genes, which when mutated are capable of bypassing the inhibition of HIS4 expression caused by a delta promoter insertion (his4-912 delta allele), was examined. Both the cre1 and cre2 mutations allowed his4-912 delta expression. ccr4 mutations were able to suppress the ability of the cre alleles to increase his4-912 delta expression. CRE2 was shown to be allelic to the SPT6 gene, and CRE1 was found to be allelic to SPT10. We suggest that the CRE genes comprise a general transcriptional control system in yeast that requires the function of the CCR4 gene.
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PMID:The CCR4 gene from Saccharomyces cerevisiae is required for both nonfermentative and spt-mediated gene expression. 240 14