High impact information on CCR4

• We demonstrate by several criteria that CCR4 and CAF1 encode critical components of the major cytoplasmic deadenylase in yeast [1].
• Mutations in the NOT genes affected many of the same genes and processes that are affected by defects in the CCR4 complex components, including reduction in ADH2 derepression, defective cell wall integrity and increased sensitivity to monoand divalent ions [2].
• The NOT proteins are part of the CCR4 transcriptional complex and affect gene expression both positively and negatively [2].
• This protein has strong sequence similarity to the C-terminal domain of the yeast transcription factor, CCR4, as well as a leucine zipper-like dimerization motif [3].
• As a component of the multisubunit CCR4 transcriptional complex, DBF2 is also involved in the regulation of gene expression [4].

Biological context of CCR4

• 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 [5].
• 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 [5].
• 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 [5].
• We now demonstrate that CCR4 encodes the catalytic subunit of the deadenylase and that Pop2p is dispensable for catalysis [6].
• The transcriptional activation ability of CCR4, in contrast to that of many other activators, was glucose regulated [7].

Associations of CCR4 with chemical compounds

• This leucine-rich repeat region may mediate the contact CCR4 makes with another factor [5].
• 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 [5].
• Strains bearing deletions in either CCR4 or CAF1/POP2, which encode components of the cytoplasmic mRNA deadenylase complex, were particularly sensitive to HU [8].

Physical interactions of CCR4

• Systematic mutagenesis of the leucine-rich repeat (LRR) domain of CCR4 reveals specific sites for binding to CAF1 and a separate critical role for the LRR in CCR4 deadenylase activity [9].

Other interactions of CCR4

• In contrast, defects in other general transcription cofactors such as CCR4, CAF1/POP2, and SNF/SWI displayed much less or no effect on LexA-ADR1-TAD activation [10].
• In contrast, CAF16, a potential ligand of CCR4, was abrogated in its binding to the LRR by mutations in the N terminus of the second beta-strand [9].
• Molecular identification of LET-711 shows it to be an ortholog of NOT1, the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels in yeast, flies, and mammals [11].

Analytical, diagnostic and therapeutic context of CCR4

• Native immunoprecipitation of CCR4 revealed that CCR4 was complexed with at least four other proteins [7].

References