Identification of four families of yCCR4- and Mg2+ -dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAFI/hPOP2 binding

被引：109

作者：

Dupressoir A. ^{[1
]}

Morel A.-P. ^{[2
]}

Barbot W. ^{[1
]}

Loireau M.-P. ^{[1
]}

Corbo L. ^{[2
]}

Heidmann T. ^{[1
]}

机构：

[1] Unite des Retrovirus Endogenes, UMR 1573 CNRS, Institut Gustave Roussy, 94805 Villejuif Cedex

[2] Biol. des Genes Suppresseurs Tumeur, INSERM U453, Centre Léon Bérard, 69373 Lyon Cedex 08

来源：

BMC Genomics | / 2卷 / 1期

关键词：

Intron Position; Dependent Endonuclease; VP16 Fusion; Domain Code Sequence; Klenow Treatment;

D O I：

10.1186/1471-2164-2-9

中图分类号：

学科分类号：

摘要：

Background: The yeast yCCR4 factor belongs to the CCR4-NOT transcriptional regulatory complex, in which it interacts, through its leucine-rich repeat (LRR) motif with yPOP2. Recently, yCCR4 was shown to be a component of the major cytoplasmic mRNA deadenylase complex, and to contain a fold related to the Mg2+-dependent endonuclease core. Results: Here, we report the identification of nineteen yCCR4-related proteins in eukaryotes (including yeast, plants and animals), which all contain the yCCR4 endonuclease-like fold, with highly conserved CCR4-specific residues. Phylogenetic and genomic analyses show that they form four distinct families, one of which contains the yCCR4 orthologs. The orthologs in animals possess a leucine-rich repeat domain. We show, using two-hybrid and far-Western assays, that the human member binds to the human yPOP2 homologs, i.e. hCAF1 and hPOP2, in a LRR-dependent manner. Conclusions: We have identified the mammalian orthologs of yCCR4 and have shown that the human member binds to the human yPOP2 homologs, thus strongly suggesting conservation of the CCR4-NOT complex from yeast to human. All members of the four identified yCCR4-related protein families show stricking conservation of the endonuclease-like catalytic motifs of the yCCR4 C-terminal domain and therefore constitute a new family of potential deadenylases in mammals. © 2001 Dupressoir et al; licensee BioMed Central Ltd.

引用

页数：14

共 34 条

[1]

Denis C.L., Identification of new genes involved in the regulation of yeast alcohol dehydrogenase II, Genetics, 108, pp. 833-843, (1984)

[2]

Liu H.-Y., Toyn J.H., Chiang Y.-C., Draper M.P., Johnson L.H., Denis C.L., DBF2, a cell cycle-regulated protein kinase, is physically and functionally associated with the CCR4 transcriptional regulatory complex, EMBO J., 16, pp. 5289-5298, (1997)

[3]

Schild D., Suppression of a new allele of the yeast RAD52 gene by over expression of RAD51, mutations in src2 and ccr4, or mating-type heterozygocity, Genetics, 140, pp. 115-127, (1995)

[4]

McKenzie E.A., Kent N.A., Dowell S.J., Moreno F., Bird L.E., Mellor J., The centromere promoter factor 1, CPF1, of Saccharomyces cerevisiae modulates gene activity through a family of factors including SPT21, RPD1 (SIN3), RPD3, and CCR4, Mol. Gen. Genet., 240, pp. 374-386, (1993)

[5]

Draper M.P., Liu H.-Y., Nelsbach A.H., Mosley S.P., Denis C.L., CCR4 is a glucose-regulated transcription factor whose leucine-rich repeat binds several proteins important for placing CCR4 in its proper promoter context, Mol. Cell. Biol., 14, pp. 4522-4531, (1994)

[6]

Liu H.-Y., Badarinarayana V., Audino D.C., Rappsilber J., Mann M., Denis C.L., The NOT proteins are part of the CCR4 transcriptional complex and affect gene expression both positively and negatively, EMBO J., 17, pp. 1096-1106, (1998)

[7]

Bai Y., Salvadore C., Chiang Y.-C., Collart M.A., Liu H.-Y., Denis C.L., The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5, Mol. Cell. Biol., 19, pp. 6642-6651, (1999)

[8]

Liu H.-Y., Chiang Y.-C., Pan J., Chan J., Salvadore C., Audino D.C., Badarinarayana V., Palaniswamy V., Anderson B., Denis C.L., Characterization of CAF4 and CAF16 reveal a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme, J. Biol. Chem., 276, pp. 7541-7548, (2001)

[9]

Chang M., French-Cornay D., Fan H.-Y., Klein H., Denis C.L., Jaehning J.A., A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling, Mol. Cell. Biol., 19, pp. 1056-1067, (1999)

[10]

Malvar T., Biron R.W., Kaback D.B., Denis C.L., The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression, Genetics, 132, pp. 951-962, (1992)

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