High impact information on POP2

• We demonstrate by several criteria that CCR4 and CAF1 encode critical components of the major cytoplasmic deadenylase in yeast [1].
• The strong conservation of Ccr4p, Caf1p, Pan2p, and Pan3p indicates that they will function as deadenylases in other eukaryotes [1].
• Unlike pol30-8, the pol30-6 and pol30-79 mutants partially reduced gene silencing at telomeres and the HMR and synergistically decreased silencing in cells lacking chromatin assembly factor 1 (CAF-1) [2].
• We purified a protein kinase that phosphorylates a peptide containing Thr 97 of Pop2p and identified it as Yak1p, a DYRK family kinase [3].
• We found that the 97th threonine residue (Thr 97) of Pop2p was phosphorylated upon glucose limitation [3].

Biological context of POP2

• We constructed POP2 deletion plasmids encoding various Pop2p regions under the native POP2 promoter and found that the minimum functional region was located in two-thirds of the carboxyl terminal region [4].
• Disruption of the CCR4 or DHH1 genes resulted in phenotypes similar to those observed for pop2 cells [5].
• Molecular analysis of POP2 gene, a gene required for glucose-derepression of gene expression in Saccharomyces cerevisiae [6].
• We isolated the POP2 gene from two yeast strains of different genetic backgrounds, S288C and A364A, and determined their nucleotide sequences [6].
• The predicted amino acid sequence of the POP2 protein contains three glutamine-rich region, a proline-rich region and a serine/threonine-rich region, characteristic of many transcription factors [6].

Associations of POP2 with chemical compounds

• Pop2 is a complex regulatory factor that participates, in part, in the repression of certain genes in the absence of glucose (Sakai, A., Chibazakura, T., Shimizu, Y., and Hishinuma, F. (1992) Nucleic Acids Res. 20, 6227-6233) [7].
• Strains bearing deletions in either CCR4 or CAF1/POP2, which encode components of the cytoplasmic mRNA deadenylase complex, were particularly sensitive to HU [8].
• CCR4, unlike all other exonuclease III family members, contains a leucine-rich repeat (LRR) motif through which it makes contact to CAF1 and other factors [9].
• Moreover, the association of CAF-1 with H3 methylated at lysine 79 appeared to occur in the late S phase [10].
• Destruction of diacetyl and acetoin occurred when the citric acid level fell to c.1000 and 600 mug/g in the case of Leuc. cremoris FR8-1 and CAF1, respectively [11].

Physical interactions of POP2

• 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].

Regulatory relationships of POP2

• In addition, yCAF1 (POP2) when fused to LexA was capable of activating transcription. mCAF1 could also activate transcription when fused to LexA and could functionally substitute for yCAF1 in allowing ADH2 expression in an spt10 mutant background [12].

Other interactions of POP2

• Similarly, ccr4, caf1 and dbf2 alleles negatively regulated FUS1-lacZ expression, as do defects in the NOT genes [13].
• MPT4 was isolated in a screen for multicopy suppressors of staurosporine sensitivity in POP2 cells [7].
• Finally, we investigated the genetic interaction between factors associated with POP2 and the PKC1 pathway [5].
• Dhh1p, a putative RNA helicase, associates with the general transcription factors Pop2p and Ccr4p from Saccharomyces cerevisiae [5].
• In addition, the rapid deadenylation of the COX17 mRNA, which is controlled by a member of the Pumilio family of deadenylation activators Puf3p, requires an active Ccr4p/Pop2p/Not deadenylase [14].

Analytical, diagnostic and therapeutic context of POP2

• Two-hybrid and immunoprecipitation data revealed that physical contact between CAF1 and the LRR is blocked by mutation of just two alpha-helix/beta-helix strand loop residues linking the first and second repeats [9].
• Site-directed mutagenesis of active-site residues demonstrates the intrinsic ability of the Pop2 RNase D domain to digest RNA [15].

References