High impact information on CDC39

• Allele-specific suppression, a two-hybrid interaction, and biochemical confractionation suggest that NOT1 and NOT2 are nuclear proteins associated in a discrete, 500-kD complex [1].
• The 195 and 185 kDa proteins were found to be NOT1 and the 116 kDa species was identical to NOT3 [2].
• CDC39, an essential nuclear protein that negatively regulates transcription and differentially affects the constitutive and inducible HIS3 promoters [3].
• By selecting for yeast strains that increase transcription by a GCN4 derivative with a defective activation domain, we have isolated a temperature-sensitive mutation in CDC39, a previously defined gene implicated in cell-cycle control and the pheromone response [3].
• CDC39 is an essential gene that encodes a very large nuclear protein (2108 amino acids) containing two glutamine-rich regions [3].

Biological context of CDC39

• These phenotypes are similar to those associated with temperature-sensitive mutations in CDC36 and CDC39, which are proposed to encode general negative regulators of transcription rather than factors involved in the pheromone response pathway [4].
• Mutations in either the CDC36 or CDC39 gene cause yeast cells to arrest in G1 of the cell cycle at the same point as treatment with mating pheromone [5].
• CDC36 and CDC39 are negative elements in the signal transduction pathway of yeast [5].
• Mutations in cell division cycle genes CDC36 and CDC39 activate the Saccharomyces cerevisiae mating pheromone response pathway [6].
• The quantities calculated for the three mRNA species were low, ranging from 1.5 +/- 1 copies per haploid cell for the CDC36 mRNA to 3.1 +/- 1.5 and 4.6 +/- 2 copies per haploid cell for the CDC37 and CDC39 mRNAs, respectively [7].

Associations of CDC39 with chemical compounds

• Taken together with our finding that Not1p copurifies with glutathione S-transferase-yTaf1 in large complexes, these results provide the first molecular evidence that the Ccr4-Not complex might interact with yTAF1 to regulate its association at promoters, a function that might in turn regulate the autoinhibitory N-terminal domain of yTAF1 [8].
• Rcd-1, a protein highly conserved across eukaryotes, was initially identified as a factor essential for nitrogen starvation-invoked differentiation in fission yeast, and its Saccharomyces cerevisiae homolog, CAF40, has been identified as part of the CCR4-NOT transcription complex, where it interacts with the NOT1 protein [9].

Regulatory relationships of CDC39

• We demonstrate here that strains harboring temperature-sensitive mutations in CDC36 or CDC39 activate expression of the pheromone-inducible gene FUS1 when shifted to nonpermissive temperature [5].
• Third, increasing the dosage of NOT1 specifically inhibited the ability of spt15-122 to suppress the his4-912delta insertion but did not affect the Spt- phenotype of spt3 or spt10 at this locus [10].

Other interactions of CDC39

• These observations suggest that Mot2 functions as a general negative regulator of transcription in the same processes as Cdc36 and Cdc39 [4].
• Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39 [7].
• The ste7, 11, and 12 mutations were not suppressed by ros1 or sst2 [11].
• 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 [12].
• Taken together, our results suggest that the Ccr4-Not complex, via the N-terminal region of Not1p, is necessary for the maintenance of stable cellular levels of Dhh1p and Caf1p, thus contributing to regulation of mRNA decay in addition to transcription [13].

References