Affiliation:
1. Department of Biochemistry and Molecular Biology, University of New Hampshire, Durham, New Hampshire 03824, 1 and
2. Département Biochimie Médicale, Centre Médical Universitaire de Genève, 1211 Geneva 4, Switzerland2
Abstract
ABSTRACT
The CCR4-NOT complex (1 mDa in size), consisting of the proteins CCR4, CAF1, and NOT1 to NOT5, regulates gene expression both positively and negatively and is distinct from other large transcriptional complexes in
Saccharomyces cerevisiae
such as SNF/SWI, TFIID, SAGA, and RNA polymerase II holoenzyme. The physical and genetic interactions between the components of the CCR4-NOT complex were investigated in order to gain insight into how this complex affects the expression of diverse genes and processes. The CAF1 protein was found to be absolutely required for CCR4 association with the NOT proteins, and CCR4 and CAF1, in turn, physically interacted with NOT1 through its central amino acid region from positions 667 to 1152. The NOT3, NOT4, and NOT5 proteins had no significant effect on the association of CCR4, CAF1, and NOT1 with each other. In contrast, the NOT2, NOT4, and NOT5 interacted with the C-terminal region (residues 1490 to 2108) of NOT1 in which NOT2 and NOT5 physically associated in the absence of CAF1, NOT3, and NOT4. These and other data indicate that the physical ordering of these proteins in the complex is CCR4-CAF1-NOT1-(NOT2, NOT5), with NOT4 and NOT3 more peripheral to NOT2 and NOT5. The physical separation of CCR4 and CAF1 from other components of the CCR4-NOT complex correlated with genetic analysis indicating partially separate functions for these two groups of proteins.
ccr4
or
caf1
deletion suppressed the increased 3-aminotriazole resistance phenotype conferred by
not
mutations, resulted in opposite effects on gene expression as compared to several
not
mutations, and resulted in a number of synthetic phenotypes in combination with
not
mutations. These results define the CCR4-NOT complex as consisting of at least two physically and functionally separated groups of proteins.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
122 articles.
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