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Functional interaction between the small GTP-binding protein Rin and the N-terminal of Brn-3a transcription factor

Abstract

Brn-3a is a transcription factor belonging to the class IV of POU domain transcription factors. It is expressed throughout the peripheral nervous system but especially in postmitotic sensory neurons of dorsal root ganglia. Brn-3a is known to regulate different genes involved in neuronal differentiation and survival. It has been shown that some of these genes require the N-terminal domain of Brn-3a in order to be activated and this effect is observed only in neurons suggesting that it may require a neuronal-specific cofactor. In order to identify this putative factor(s) we screened a cDNA library via a variant of the original yeast two-hybrid system. By using the N-terminal of Brn-3a as the bait, we have repeatedly isolated a protein named Rin, an incompletely characterized small GTP-binding protein expressed only in neurons. In this work, we describe the evidence for a functional interaction between Brn-3a and Rin and demonstrate the role of Rin in modulating the activation of the Brn-3a regulated egr-1 promoter by the N-terminal domain of Brn-3a.

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References

  • Aronheim A, Zandi E, Hennemann H, Elledge SJ and Karin M . (1997). Mol. Cell. Biol., 17, 3094–3102.

    Article  CAS  Google Scholar 

  • Casey PJ . (1995). Science, 268, 221–225.

    Article  CAS  Google Scholar 

  • Ensor E, Smith MD and Latchman DS . (2001). J. Biol. Chem., 276, 5204–5212.

  • Fedtsova NG and Turner EE . (1995). Mech. Dev., 53, 291–304.

  • Fields S and Song OK . (1989). Nature, 340, 245–246.

    Article  CAS  Google Scholar 

  • Gerrero MR, McEvilly RJ, Turner E, Lin CR, O'Connell S, Jenne KJ, Hobbs MV and Rosenfeld MG . (1993). Proc. Natl. Acad. Sci. USA, 90, 10841–10845.

  • Gorman CM . (1985). DNA Cloning: A Practical Approach, Vol 2. Glover DM (ed) IRL Press at Oxford University Press: Oxford, pp. 143–190.

    Google Scholar 

  • He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW and Rosenfeld MG . (1989). Nature, 340, 35–41.

    Article  CAS  Google Scholar 

  • Lakin ND, Morris PJ, Theil T, Sato TN, Moroy T, Wilson MC and Latchman DS . (1995). J. Biol. Chem., 270, 15858–15863.

    Article  CAS  Google Scholar 

  • Lee CH, Dellia NG, Chew CE and Zack DJ . (1996). J. Neurosci., 16, 6784–6794.

    Article  CAS  Google Scholar 

  • Lillycrop KA, Budrahan VS, Lakin ND, Terrenghi G, Wood JN, Polak JM and Latchman DS . (1992). Nucleic Acids Res., 20, 5093–5096.

  • Liu YZ, Dawson SJ and Latchman DS . (1996). J. Mol. Neurosci., 7, 77–85 (1997).

  • Morris PJ, Lakin ND, Dawson SJ, Ryabinin AE, Kilimann MW, Wilson MC and Latchman DS . (1996). Brain Res. Mol. Brain Res., 43, 279–285.

  • Ninkina NN, Stevens GE, Wood JN and Richardson WD . (1993). Nucleic Acids Res., 21, 3175–3182.

  • Patel G, Macdonald MJ, Khosravi-Far R, Hisaka MM and Der CJ . (1992). Oncogene, 7, 283–288.

  • Rusyn EV, Reynolds ER, Shao H, Grana TM, Chan TO, Andres DA and Cox AD. (2000). Oncogene, 19, 4685–4694.

    Article  CAS  Google Scholar 

  • Shao H, Kadono-Okuda K, Finlin BS and Andres DA . (1999). Arch. Biochem. Biophys., 371, 207–219.

  • Smith MD, Dawson SJ, Boxer LM and Latchman DS . (1998a). Nucleic Acids Res., 26, 4100–4107.

  • Smith MD, Dawson SJ and Latchman DS . (1997). Mol. Cell. Biol., 17, 345–354.

    Article  CAS  Google Scholar 

  • Smith MD, Ensor EA, Coffin RS, Boxer LM and Latchman DS . (1998b). J. Biol. Chem., 273, 16715–16722.

    Article  CAS  Google Scholar 

  • Smith MD, Ensor EA, Stohl L, Wagner JA and Latchman DS . (1999). Brain Res. Mol. Brain Res., 74, 117–125.

  • Smith MD, Melton LA, Ensor EA, Packham G, Anderson P, Kinloch RA and Latchman DS . (2001). Mol. Cell. Neurosci., 17, 460–470.

  • Spencer ML, Shao H, Tucker HM and Andres DA . (2002). J. Biol. Chem., 277, 17605–17615.

    Article  CAS  Google Scholar 

  • Theil T, Mclean-Hunter S, Zornig M and Moroy T . (1993). Nucleic Acids Res., 21, 5921–5929.

  • Xiang M . (1998). Dev. Biol., 197, 155–169.

  • Xiang M, Gan L, Li D, Chen ZY, Zhou L, O'Malley Jr BW, Klein W and Nathans J . (1997). Proc. Natl. Acad. Sci. USA, 94, 9445–9450.

  • Xiang M, Gan L, Zhou L, Klein WH and Nathans J . (1996). Proc. Natl. Acad. Sci. USA, 93, 11950–11955.

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Acknowledgements

A special acknowledgement to Ms Shazia Irshad for providing the stable cell line overexpressing Brn-3a and to Dr Martin P Smith for the scientific discussion throughout the course of the experiments. This work was supported by the Wellcome Trust. MC gratefully acknowledges the financial support of Telethon-Italy (Grant No. 487/b).

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Correspondence to M Calissano.

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Calissano, M., Latchman, D. Functional interaction between the small GTP-binding protein Rin and the N-terminal of Brn-3a transcription factor. Oncogene 22, 5408–5414 (2003). https://doi.org/10.1038/sj.onc.1206635

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