Structural highlights
Function[CNOT7_HUMAN] Ubiquitous transcription factor required for a diverse set of processes. It is a component of the CCR4 complex involved in the control of gene expression (By similarity). [TOB1_HUMAN] Anti-proliferative protein that interacts with the erbB-2 receptor tyrosine kinase. May physically and/or functionally interact with protein-tyrosine kinase receptors. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Tob/BTG family is a group of antiproliferative proteins containing two highly homologous regions, Box A and Box B. These proteins all associate with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D (RNase D) family of deadenylases and is a component of the CCR4-Not deadenylase complex. Here we determined the crystal structure of the complex of the N-terminal region of Tob and human Caf1 (hCaf1). Tob exhibited a novel fold, whereas hCaf1 most closely resembled the catalytic domain of yeast Pop2 and human poly(A)-specific ribonuclease. Interestingly, the association of hCaf1 was mediated by both Box A and Box B of Tob. Cell growth assays using both wild-type and mutant proteins revealed that deadenylase activity of Caf1 is not critical but complex formation is crucial to cell growth inhibition. Caf1 tethers Tob to the CCR4-Not deadenylase complex, and thereby Tob gathers several factors at its C-terminal region, such as poly(A)-binding proteins, to exert antiproliferative activity. Structural basis for the antiproliferative activity of the Tob-hCaf1 complex.,Horiuchi M, Takeuchi K, Noda N, Muroya N, Suzuki T, Nakamura T, Kawamura-Tsuzuku J, Takahasi K, Yamamoto T, Inagaki F J Biol Chem. 2009 May 8;284(19):13244-55. Epub 2009 Mar 10. PMID:19276069[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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