Skip to main content

BTG/TOB

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

Synonyms

BTG1; BTG2 (TIS21, PC3); BTG3 (ANA, TOB5); BTG4 (PC3B); TOB1 (TOB, Transducer of ERBB2); TOB2 (Transducer of ERBB2 2)

Historical Background

The human BTG/Tob proteins form a small family of six proteins, which share a conserved N-terminal domain and antiproliferative activity (Matsuda et al. 2001; Tirone 2001; Winkler 2010). BTG2 was discovered first by two laboratories: as the immediate/early response gene PC3 in rat PC12 cells stimulated with nerve growth factor (NGF) and as TIS21 in mouse 3T3 fibroblasts in response to treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). The discovery of BTG1 (B-cell translocation gene 1) as a gene involved in a chromosomal translocation associated with chronic lymphocytic leukemia suggested the presence of a new family of antiproliferative genes. These findings were extended by the discovery of TOB1, which was found as an interacting protein of the ErbB2 tyrosine-kinase receptor (HER2). The remaining three members BTG3 (ANA), BTG4...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, et al. Osteoporotic bone formation in mice lacking tob2: involvement of Tob2 in RANK ligand expression and osteoclasts differentiation. FEBS Lett. 2008;582:1313–8. doi:10.1016/j.febslet.2008.03.012. , S0014-5793(08)00241-X [pii]

    Article  CAS  PubMed  Google Scholar 

  • Boiko AD, Porteous S, Razorenova OV, Krivokrysenko VI, Williams BR, Gudkov AV. A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation. Genes Dev. 2006;20:236–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ezzeddine N, Chang TC, Zhu W, Yamashita A, Chen CY, Zhong Z, et al. Human TOB, an antiproliferative transcription factor, is a poly(A)-binding protein-dependent positive regulator of cytoplasmic mRNA deadenylation. Mol Cell Biol. 2007;27:7791–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, et al. Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases. Genes Dev. 2007;21:3135–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horiuchi M, Takeuchi K, Noda N, Muroya N, Suzuki T, Nakamura T, et al. Structural basis for the antiproliferative activity of the Tob-hCaf1 complex. J Biol Chem. 2009;284:13244–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hosoda N, Funakoshi Y, Hirasawa M, Yamagishi R, Asano Y, Miyagawa R, et al. Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase. EMBO J. 2011;30:1311–23. doi:10.1038/emboj.2011.37. , emboj201137 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda S, Rouault J, Magaud J, Berthet C. In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett. 2001;497:67–72.

    Article  CAS  PubMed  Google Scholar 

  • Mauxion F, Chen CY, Seraphin B, Shyu AB. BTG/TOB factors impact deadenylases. Trends Biochem Sci. 2009;34:640–7. doi:10.1016/j.tibs.2009.07.008 , S0968-0004(09)00170-4 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyai K, Yoneda M, Hasegawa U, Toita S, Izu Y, Hemmi H, et al. ANA deficiency enhances bone morphogenetic protein-induced ectopic bone formation via transcriptional events. J Biol Chem. 2009;284:10593–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ou YH, Chung PH, Hsu FF, Sun TP, Chang WY, Shieh SY. The candidate tumor suppressor BTG3 is a transcriptional target of p53 that inhibits E2F1. EMBO J. 2007;26:3968–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park S, Lee YJ, Lee HJ, Seki T, Hong KH, Park J, et al. B-cell translocation gene 2 (Btg2) regulates vertebral patterning by modulating bone morphogenetic protein/smad signaling. Mol Cell Biol. 2004;24:10256–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rouault JP, Falette N, Guehenneux F, Guillot C, Rimokh R, Wang Q, et al. Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Nat Genet. 1996;14:482–6.

    Article  CAS  PubMed  Google Scholar 

  • Stupfler B, Birck C, Seraphin B, Mauxion F. BTG2 bridges PABPC1 RNA-binding domains and CAF1 deadenylase to control cell proliferation. Nat Commun. 2016;7:10811. doi:10.1038/ncomms10811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki T, J KT, 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 Dev. 2002;16:1356–70.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tirone F. The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair? J Cell Physiol. 2001;187:155–65.

    Article  CAS  PubMed  Google Scholar 

  • Usui M, Yoshida Y, Tsuji K, Oikawa K, Miyazono K, Ishikawa I, et al. Tob deficiency superenhances osteoblastic activity after ovariectomy to block estrogen deficiency-induced osteoporosis. Proc Natl Acad Sci U S A 2004;101:6653–6658. doi:10.1073/pnas.0303093101, 0303093101 [pii].

    Google Scholar 

  • Washio-Oikawa K, Nakamura T, Usui M, Yoneda M, Ezura Y, Ishikawa I, et al. Cnot7-null mice exhibit high bone mass phenotype and modulation of BMP actions. J Bone Miner Res. 2007;22:1217–23.

    Article  PubMed  Google Scholar 

  • Winkler GS. The mammalian anti-proliferative BTG/Tob protein family. J Cell Physiol. 2010;222:66–72. doi:10.1002/jcp.21919.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida Y, Nakamura T, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, et al. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 2003;17:1201–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gerlof Sebastiaan Winkler .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Almasmoum, H., Doidge, R., Winkler, G.S. (2016). BTG/TOB. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_272-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_272-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics