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.[7]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Matsuda S, Kawamura-Tsuzuku J, Ohsugi M, Yoshida M, Emi M, Nakamura Y, Onda M, Yoshida Y, Nishiyama A, Yamamoto T (Feb 1996). "Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity".Oncogene.12 (4):705–13.PMID8632892.
^Ikematsu N, Yoshida Y, Kawamura-Tsuzuku J, Ohsugi M, Onda M, Hirai M, Fujimoto J, Yamamoto T (Dec 1999). "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.doi:10.1038/sj.onc.1203193.PMID10602502.S2CID35769674.
^Jin Cho S, La M, Ahn JK, Meadows GG, Joe CO (May 2001). "Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation".Biochemical and Biophysical Research Communications.283 (2):273–7.doi:10.1006/bbrc.2001.4773.PMID11327693.
Sasaki S, Imai K (Mar 2002). "[Monoclonal antibody induces apoptosis against cancer cells]".Nihon Rinsho. Japanese Journal of Clinical Medicine.60 (3):451–6.PMID11904957.
Ikematsu N, Yoshida Y, Kawamura-Tsuzuku J, Ohsugi M, Onda M, Hirai M, Fujimoto J, Yamamoto T (Dec 1999). "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.doi:10.1038/sj.onc.1203193.PMID10602502.S2CID35769674.
Jin Cho S, La M, Ahn JK, Meadows GG, Joe CO (May 2001). "Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation".Biochemical and Biophysical Research Communications.283 (2):273–7.doi:10.1006/bbrc.2001.4773.PMID11327693.
Tzachanis D, Freeman GJ, Hirano N, van Puijenbroek AA, Delfs MW, Berezovskaya A, Nadler LM, Boussiotis VA (Dec 2001). "Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells".Nature Immunology.2 (12):1174–82.doi:10.1038/ni730.PMID11694881.S2CID38103879.
Sasajima H, Nakagawa K, Yokosawa H (Jul 2002). "Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system".European Journal of Biochemistry.269 (14):3596–604.doi:10.1046/j.1432-1033.2002.03052.x.PMID12135500.
Yoshida Y, von Bubnoff A, Ikematsu N, Blitz IL, Tsuzuku JK, Yoshida EH, Umemori H, Miyazono K, Yamamoto T, Cho KW (May 2003). "Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling".Mechanisms of Development.120 (5):629–37.doi:10.1016/S0925-4773(03)00020-0.PMID12782279.S2CID728736.
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 (Dec 2003). "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.doi:10.1016/j.canlet.2003.08.019.PMID14643028.
Maekawa M, Yamamoto T, Nishida E (Apr 2004). "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.doi:10.1016/j.yexcr.2003.12.016.PMID15051490.
Kawamura-Tsuzuku J, Suzuki T, Yoshida Y, Yamamoto T (Aug 2004). "Nuclear localization of Tob is important for regulation of its antiproliferative activity".Oncogene.23 (39):6630–8.doi:10.1038/sj.onc.1207890.PMID15235587.S2CID19519175.
