The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex
The human BTG/TOB protein family comprises six members (BTG1, BTG2/PC3/Tis21, BTG3/Ana, BTG4/PC3B, TOB1/Tob, and TOB2) that are characterised by a conserved BTG domain. This domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deaden...
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| description | The human BTG/TOB protein family comprises six members (BTG1, BTG2/PC3/Tis21, BTG3/Ana, BTG4/PC3B, TOB1/Tob, and TOB2) that are characterised by a conserved BTG domain. This domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deadenylase complex. BTG/TOB proteins have anti-proliferative activity: knockdown of BTG/TOB can result in increased cell proliferation, whereas over-expression of BTG/TOB leads to inhibition of cell cycle progression. It was unclear whether the interaction between BTG/TOB proteins and the Caf1a/Caf1b deadenylases is necessary for the anti-proliferative activity of BTG/TOB. To address this question, we further characterised surface-exposed amino acid residues of BTG2 and TOB1 that mediate the interaction with the Caf1a and Caf1b deadenylase enzymes. We then analysed the role of BTG2 and TOB1 in the regulation of cell proliferation, translation and mRNA abundance using a mutant that is no longer able to interact with the Caf1a/Caf1b deadenylases. We conclude that the anti-proliferative activity of BTG/TOB proteins is mediated through interactions with the Caf1a and Caf1b deadenylase enzymes. Furthermore, we show that the activity of BTG/TOB proteins in the regulation of mRNA abundance and translation is dependent on Caf1a/Caf1b, and does not appear to require other Ccr4-Not components, including the Ccr4a (CNOT6)/Ccr4b (CNOT6L) deadenylases, or the non-catalytic subunits CNOT1 or CNOT3. |
| doi_str_mv | 10.1371/journal.pone.0051331 |
| format | Article |
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This domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deadenylase complex. BTG/TOB proteins have anti-proliferative activity: knockdown of BTG/TOB can result in increased cell proliferation, whereas over-expression of BTG/TOB leads to inhibition of cell cycle progression. It was unclear whether the interaction between BTG/TOB proteins and the Caf1a/Caf1b deadenylases is necessary for the anti-proliferative activity of BTG/TOB. To address this question, we further characterised surface-exposed amino acid residues of BTG2 and TOB1 that mediate the interaction with the Caf1a and Caf1b deadenylase enzymes. We then analysed the role of BTG2 and TOB1 in the regulation of cell proliferation, translation and mRNA abundance using a mutant that is no longer able to interact with the Caf1a/Caf1b deadenylases. We conclude that the anti-proliferative activity of BTG/TOB proteins is mediated through interactions with the Caf1a and Caf1b deadenylase enzymes. Furthermore, we show that the activity of BTG/TOB proteins in the regulation of mRNA abundance and translation is dependent on Caf1a/Caf1b, and does not appear to require other Ccr4-Not components, including the Ccr4a (CNOT6)/Ccr4b (CNOT6L) deadenylases, or the non-catalytic subunits CNOT1 or CNOT3.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0051331</identifier><identifier>PMID: 23236473</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abundance ; Amino Acid Motifs - genetics ; Amino acids ; Antiproliferatives ; Apoptosis ; Biology ; Breast cancer ; BTG2 protein ; Catalysis ; Catalytic subunits ; Cell cycle ; Cell Cycle - genetics ; Cell Cycle - physiology ; Cell growth ; Cell Proliferation ; Cloning ; DNA Primers - genetics ; DNA, Complementary - genetics ; Enzymes ; Fluorescent Antibody Technique ; Gene Knockdown Techniques ; Genes ; HEK293 Cells ; Humans ; Immediate-Early Proteins - genetics ; Immediate-Early Proteins - metabolism ; Immunoprecipitation ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinases ; mRNA ; Mutagenesis ; Mutation ; Overexpression ; Pharmacy ; Phosphorylation ; Plasmids ; Plasmids - genetics ; Polymerase Chain Reaction ; Proteins ; RNA, Small Interfering - genetics ; Sequence Analysis, DNA ; Transcription Factors - metabolism ; Translation ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Two-Hybrid System Techniques</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e51331</ispartof><rights>2012 Doidge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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This domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deadenylase complex. BTG/TOB proteins have anti-proliferative activity: knockdown of BTG/TOB can result in increased cell proliferation, whereas over-expression of BTG/TOB leads to inhibition of cell cycle progression. It was unclear whether the interaction between BTG/TOB proteins and the Caf1a/Caf1b deadenylases is necessary for the anti-proliferative activity of BTG/TOB. To address this question, we further characterised surface-exposed amino acid residues of BTG2 and TOB1 that mediate the interaction with the Caf1a and Caf1b deadenylase enzymes. We then analysed the role of BTG2 and TOB1 in the regulation of cell proliferation, translation and mRNA abundance using a mutant that is no longer able to interact with the Caf1a/Caf1b deadenylases. We conclude that the anti-proliferative activity of BTG/TOB proteins is mediated through interactions with the Caf1a and Caf1b deadenylase enzymes. 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This domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deadenylase complex. BTG/TOB proteins have anti-proliferative activity: knockdown of BTG/TOB can result in increased cell proliferation, whereas over-expression of BTG/TOB leads to inhibition of cell cycle progression. It was unclear whether the interaction between BTG/TOB proteins and the Caf1a/Caf1b deadenylases is necessary for the anti-proliferative activity of BTG/TOB. To address this question, we further characterised surface-exposed amino acid residues of BTG2 and TOB1 that mediate the interaction with the Caf1a and Caf1b deadenylase enzymes. We then analysed the role of BTG2 and TOB1 in the regulation of cell proliferation, translation and mRNA abundance using a mutant that is no longer able to interact with the Caf1a/Caf1b deadenylases. We conclude that the anti-proliferative activity of BTG/TOB proteins is mediated through interactions with the Caf1a and Caf1b deadenylase enzymes. Furthermore, we show that the activity of BTG/TOB proteins in the regulation of mRNA abundance and translation is dependent on Caf1a/Caf1b, and does not appear to require other Ccr4-Not components, including the Ccr4a (CNOT6)/Ccr4b (CNOT6L) deadenylases, or the non-catalytic subunits CNOT1 or CNOT3.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23236473</pmid><doi>10.1371/journal.pone.0051331</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2012-12, Vol.7 (12), p.e51331 |
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| subjects | Abundance Amino Acid Motifs - genetics Amino acids Antiproliferatives Apoptosis Biology Breast cancer BTG2 protein Catalysis Catalytic subunits Cell cycle Cell Cycle - genetics Cell Cycle - physiology Cell growth Cell Proliferation Cloning DNA Primers - genetics DNA, Complementary - genetics Enzymes Fluorescent Antibody Technique Gene Knockdown Techniques Genes HEK293 Cells Humans Immediate-Early Proteins - genetics Immediate-Early Proteins - metabolism Immunoprecipitation Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Kinases mRNA Mutagenesis Mutation Overexpression Pharmacy Phosphorylation Plasmids Plasmids - genetics Polymerase Chain Reaction Proteins RNA, Small Interfering - genetics Sequence Analysis, DNA Transcription Factors - metabolism Translation Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Two-Hybrid System Techniques |
| title | The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T08%3A31%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20anti-proliferative%20activity%20of%20BTG/TOB%20proteins%20is%20mediated%20via%20the%20Caf1a%20(CNOT7)%20and%20Caf1b%20(CNOT8)%20deadenylase%20subunits%20of%20the%20Ccr4-not%20complex&rft.jtitle=PloS%20one&rft.au=Doidge,%20Rachel&rft.date=2012-12-07&rft.volume=7&rft.issue=12&rft.spage=e51331&rft.pages=e51331-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0051331&rft_dat=%3Cproquest_plos_%3E2952579161%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1339065005&rft_id=info:pmid/23236473&rft_doaj_id=oai_doaj_org_article_a836381a96d84cff820449e17084e6d3&rfr_iscdi=true |