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 PubMed
The 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
- ↑ Horiuchi M, Takeuchi K, Noda N, Muroya N, Suzuki T, Nakamura T, Kawamura-Tsuzuku J, Takahasi K, Yamamoto T, Inagaki F. Structural basis for the antiproliferative activity of the Tob-hCaf1 complex. J Biol Chem. 2009 May 8;284(19):13244-55. Epub 2009 Mar 10. PMID:19276069 doi:10.1074/jbc.M809250200
