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Dr Stephen A Wood
Child Health Research Institute
University of Adelaide
72 King William Road, North Adelaide, SA 5006
Email: stephen.wood@adelaide.edu.au
Tel: +61-8-8161-7078
Fax: +61-8-8239-0267 or 2103
Homepage: http://www.chri.com.au/StemCellBiology.htm

Ubiquitylated substrates can be deubiquitylated by Ubiquitin-specific proteases (UBPs). Some Ubps function downstream of the proteasome and have little substrate specificity and simply recycle the ubiquitin moiety. However a class of substrate-specific Ubps function upstream of the
proteasome and represent another level of control and maintain intracellular substrate pools.
The murine deubiquitylating enzyme FAM is a developmentally regulated substrate-specific UBP. In mammalian cells, biochemical studies have identified interactions between FAM and the cell-adhesion and signalling molecules, AF-6 and b-catenin. AF-6 and FAM physically interact and co-localise at tight junctions in polarised MDCK cells. Exogenous Fam expression decreases the level of AF-6 ubiquitylation. In MDCK cells FAM is also present at the adherens junction where it interacts with b-catenin. FAM can also extend the half-life of b-catenin in COS cells. Together these data suggest a role for FAM in regulating cell adhesive events in epithelial cells. We have confirmed this hypothesis by deleting FAM in preimplantation mouse embryos where loss of FAM results in loss of cell adhesion and depletion of both b-catenin and AF-6.
Dr Richard D'Andrea Child Health Research Institute
Dr Peter McPherson Montreal Neurological Institute
Professor Rolf Kemler Max-Planck Institute, Freiburg
Taya, S., T. Yamamoto, K. Kano, Y. Kawano, A. Iwamatsu, T. Tsuchiya, T. Tanaka, M. Kanai-Azuma., S.A. Wood, J.S. Mattick and K. Kaibuchi (1998) The Ras target AF-6 is a physiological substrate of the Fam deubiquitinating
enzyme. Journal of Cell Biology, 142, 1053 - 1062.

Taya, S., T. Yamamoto, M. Kanai-Azuma, S.A. Wood and K. Kaibuchi (1999) The deubiquitinating enzyme Fam interacts with and stabilizes beta-catenin. Genes to Cells 4, 757 - 767.

Pantaleon, M., M. Kanai-Azuma, J.S. Mattick, K. Kaibuchi, P.L. Kaye and S.A. Wood (2001) FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development. Mechanisms of Development, 109, 151 - 160.
development and oogenesis in mice. Mechanisms of Development, 119S, S91 - S95.

S. A. Wood, (2002) Dubble or nothing Is HAUSP deubiquitylating enzyme the final arbiter of p53 levels. Science's STKE www.stke.org/cgi/content/full/sigtrans;2002/143/pe34

Murray, R.Z., Jolly, L.A. and Wood, S.A. (2004) The FAM deubiquitylating enzyme localises to multiple points of protein trafficking where it associates with E-cadherin and b-catenin. Molecular Biology of the Cell, in press

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