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The LIM Domain Protein LPP Is a Coactivator for the ETS Domain Transcription Factor PEA3

Baoqiang Guo,¹ Rosemary E. Sallis,^1, Amanda Greenall,² Marleen M. R. Petit,³ Erik Jansen,^3, Leonie Young,⁴ Wim J. M. Van de Ven,³ and Andrew D. Sharrocks^1*

Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom,¹ School of Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kindgom,² Laboratory for Molecular Oncology, Department of Human Genetics, Katholieke Universiteit Leuven and VIB, Herestraat 49, B-3000 Leuven, Belgium,³ Conway Institute, UCD, Belfield, Dublin 4, Ireland⁴

Received 26 August 2005/ Returned for modification 21 September 2005/ Accepted 22 March 2006

PEA3 is a member of a subfamily of ETS domain transcription factors which is regulated by a number of signaling cascades, including the mitogen-activated protein (MAP) kinase pathways. PEA3 activates gene expression and is thought to play an important role in promoting tumor metastasis and also in neuronal development. Here, we have identified the LIM domain protein LPP as a novel coregulatory binding partner for PEA3. LPP has intrinsic transactivation capacity, forms a complex with PEA3, and is found associated with PEA3-regulated promoters. By manipulating LPP levels, we show that it acts to upregulate the transactivation capacity of PEA3. LPP can also functionally interact in a similar manner with the related family member ER81. Thus, we have uncovered a novel nuclear function for the LIM domain protein LPP as a transcriptional coactivator. As LPP continually shuttles between the cell periphery and the nucleus, it represents a potential novel link between cell surface events and changes in gene expression.

Present address: Department of Pathology, Veterinary Laboratories Agency-Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom.

Present address: Global Business Intelligence Center, N.V. Organon, Oss, The Netherlands.

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