TOB1 explained

Protein Tob1 is a protein that in humans is encoded by the TOB1 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the tob/btg1 family of anti-proliferative proteins that have the potential to regulate cell growth. When exogenously expressed, this protein suppresses cell growth in tissue culture. The protein undergoes phosphorylation by a serine/threonine kinase, 90 kDa ribosomal S6 kinase. Interactions of this protein with the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 gene product p185 interferes with growth suppression. This protein inhibits T cell proliferation and transcription of cytokines and cyclins. The protein interacts with both mothers against decapentaplegic Drosophila homolog 2 and 4 to enhance their DNA binding activity. This interaction inhibits interleukin 2 transcription in T cells.^[3]

Interactions

TOB1 has been shown to interact with:

• CNOT7,^{[4] [5]}
• MAPK1^[6]
• MARCKS,^[7]
• Mitogen-activated protein kinase 9,^[6] and
• RPS6KA1.^[8]

Further reading

• Sasaki S, Imai K . [Monoclonal antibody induces apoptosis against cancer cells] . Nihon Rinsho. Japanese Journal of Clinical Medicine . 60 . 3 . 451–6 . Mar 2002 . 11904957 .
• Yoshida Y, Matsuda S, Yamamoto T . Cloning and characterization of the mouse tob gene . Gene . 191 . 1 . 109–13 . May 1997 . 9210596 . 10.1016/S0378-1119(97)00049-8 .
• Ikematsu N, Yoshida Y, Kawamura-Tsuzuku J, Ohsugi M, Onda M, Hirai M, Fujimoto J, Yamamoto T . Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases . Oncogene . 18 . 52 . 7432–41 . Dec 1999 . 10602502 . 10.1038/sj.onc.1203193 . 35769674 .
• Yoshida Y, Tanaka S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T . Negative regulation of BMP/Smad signaling by Tob in osteoblasts . Cell . 103 . 7 . 1085–97 . Dec 2000 . 11163184 . 10.1016/S0092-8674(00)00211-7 . 18267832 . free .
• Suzuki T, Matsuda S, Tsuzuku JK, Yoshida Y, Yamamoto T . A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob . Genes to Cells . 6 . 2 . 131–8 . Feb 2001 . 11260258 . 10.1046/j.1365-2443.2001.00406.x . 21599032 . free .
• Jin Cho S, La M, Ahn JK, Meadows GG, Joe CO . Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation . Biochemical and Biophysical Research Communications . 283 . 2 . 273–7 . May 2001 . 11327693 . 10.1006/bbrc.2001.4773 .
• Yoshida Y, Hosoda E, Nakamura T, Yamamoto T . Association of ANA, a member of the antiproliferative Tob family proteins, with a Caf1 component of the CCR4 transcriptional regulatory complex . Japanese Journal of Cancer Research . 92 . 6 . 592–6 . Jun 2001 . 11429045 . 10.1111/j.1349-7006.2001.tb01135.x . 5926753 .
• Tzachanis D, Freeman GJ, Hirano N, van Puijenbroek AA, Delfs MW, Berezovskaya A, Nadler LM, Boussiotis VA . Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells . Nature Immunology . 2 . 12 . 1174–82 . Dec 2001 . 11694881 . 10.1038/ni730 . 38103879 .
• Suzuki T, K-Tsuzuku J, Ajima R, Nakamura T, Yoshida Y, Yamamoto T . Phosphorylation of three regulatory serines of Tob by Erk1 and Erk2 is required for Ras-mediated cell proliferation and transformation . Genes & Development . 16 . 11 . 1356–70 . Jun 2002 . 12050114 . 186319 . 10.1101/gad.962802 .
• Sasajima H, Nakagawa K, Yokosawa H . Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system . European Journal of Biochemistry . 269 . 14 . 3596–604 . Jul 2002 . 12135500 . 10.1046/j.1432-1033.2002.03052.x .
• Maekawa M, Nishida E, Tanoue T . Identification of the Anti-proliferative protein Tob as a MAPK substrate . The Journal of Biological Chemistry . 277 . 40 . 37783–7 . Oct 2002 . 12151396 . 10.1074/jbc.M204506200 . free .
• Yoshida Y, von Bubnoff A, Ikematsu N, Blitz IL, Tsuzuku JK, Yoshida EH, Umemori H, Miyazono K, Yamamoto T, Cho KW . Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling . Mechanisms of Development . 120 . 5 . 629–37 . May 2003 . 12782279 . 10.1016/S0925-4773(03)00020-0 . 728736 .
• Iwanaga K, Sueoka N, Sato A, Sakuragi T, Sakao Y, Tominaga M, Suzuki T, Yoshida Y, K-Tsuzuku J, Yamamoto T, Hayashi S, Nagasawa K, Sueoka E . Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer . Cancer Letters . 202 . 1 . 71–9 . Dec 2003 . 14643028 . 10.1016/j.canlet.2003.08.019 .
• Maekawa M, Yamamoto T, Nishida E . Regulation of subcellular localization of the antiproliferative protein Tob by its nuclear export signal and bipartite nuclear localization signal sequences . Experimental Cell Research . 295 . 1 . 59–65 . Apr 2004 . 15051490 . 10.1016/j.yexcr.2003.12.016 .
• Kawamura-Tsuzuku J, Suzuki T, Yoshida Y, Yamamoto T . Nuclear localization of Tob is important for regulation of its antiproliferative activity . Oncogene . 23 . 39 . 6630–8 . Aug 2004 . 15235587 . 10.1038/sj.onc.1207890 . 19519175 .
• Okochi K, Suzuki T, Inoue J, Matsuda S, Yamamoto T . Interaction of anti-proliferative protein Tob with poly(A)-binding protein and inducible poly(A)-binding protein: implication of Tob in translational control . Genes to Cells . 10 . 2 . 151–63 . Feb 2005 . 15676026 . 10.1111/j.1365-2443.2005.00826.x . 40563615 . free .

Notes and References

1. Matsuda S, Kawamura-Tsuzuku J, Ohsugi M, Yoshida M, Emi M, Nakamura Y, Onda M, Yoshida Y, Nishiyama A, Yamamoto T . Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity . Oncogene . 12 . 4 . 705–13 . Feb 1996 . 8632892 .
2. Ezzeddine N, Chang TC, Zhu W, Yamashita A, Chen CY, Zhong Z, Yamashita Y, Zheng D, Shyu AB . Human TOB, an antiproliferative transcription factor, is a poly(A)-binding protein-dependent positive regulator of cytoplasmic mRNA deadenylation . Molecular and Cellular Biology . 27 . 22 . 7791–801 . Nov 2007 . 17785442 . 2169145 . 10.1128/MCB.01254-07 .
3. Web site: Entrez Gene: TOB1 transducer of ERBB2, 1.
4. Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, Tsujimoto M, Suzuki T, Katada T, Hoshino S . Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases . Genes & Development . 21 . 23 . 3135–48 . Dec 2007 . 18056425 . 2081979 . 10.1101/gad.1597707 .
5. Ikematsu N, Yoshida Y, Kawamura-Tsuzuku J, Ohsugi M, Onda M, Hirai M, Fujimoto J, Yamamoto T . Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases . Oncogene . 18 . 52 . 7432–41 . Dec 1999 . 10602502 . 10.1038/sj.onc.1203193 . 35769674 .
6. Maekawa M, Nishida E, Tanoue T . Identification of the Anti-proliferative protein Tob as a MAPK substrate . The Journal of Biological Chemistry . 277 . 40 . 37783–7 . Oct 2002 . 12151396 . 10.1074/jbc.M204506200 . free .
7. Jin Cho S, La M, Ahn JK, Meadows GG, Joe CO . Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation . Biochemical and Biophysical Research Communications . 283 . 2 . 273–7 . May 2001 . 11327693 . 10.1006/bbrc.2001.4773 .
8. Suzuki T, Matsuda S, Tsuzuku JK, Yoshida Y, Yamamoto T . A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob . Genes to Cells . 6 . 2 . 131–8 . Feb 2001 . 11260258 . 10.1046/j.1365-2443.2001.00406.x. 21599032 . free .