PDSM, a motif for phosphorylation-dependent SUMO modification

doi:10.1073/pnas.0503698102

PDSM, a motif for phosphorylation-dependent SUMO modification

^*Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20521, Turku, Finland; ^†Department of Biology, Åbo Akademi University, FI-20520, Turku, Finland; ^∥Department of Medical Biochemistry, University of Kuopio, FI-70211, Kuopio, Finland; ^**Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, FI-00014, Helsinki, Finland; and ^¶Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube 755-8505, Japan

Edited by Peter Walter, University of California School of Medicine, San Francisco, CA, and approved November 3, 2005 (received for review May 4, 2005)

Abstract

SUMO (small ubiquitin-like modifier) modification regulates many cellular processes, including transcription. Although sumoylation often occurs on specific lysines within the consensus tetrapeptide ΨKxE, other modifications, such as phosphorylation, may regulate the sumoylation of a substrate. We have discovered PDSM (phosphorylation-dependent sumoylation motif), composed of a SUMO consensus site and an adjacent proline-directed phosphorylation site (ΨKxExxSP). The highly conserved motif regulates phosphorylation-dependent sumoylation of multiple substrates, such as heat-shock factors (HSFs), GATA-1, and myocyte enhancer factor 2. In fact, the majority of the PDSM-containing proteins are transcriptional regulators. Within the HSF family, PDSM is conserved between two functionally distinct members, HSF1 and HSF4b, whose transactivation capacities are repressed through the phosphorylation-dependent sumoylation. As the first recurrent sumoylation determinant beyond the consensus tetrapeptide, the PDSM provides a valuable tool in predicting new SUMO substrates.

Footnotes

↵ †† To whom correspondence should be addressed at: Turku Centre for Biotechnology, P.O. Box 123, FI-20521, Turku, Finland. E-mail: lea.sistonen{at}btk.fi.
↵ ‡ V.H. and J.A. contributed equally to this work.
↵ § Present address: European Molecular Biology Laboratory, Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Author contributions: V.H., J.A., H.A.B., J.J.P., A.N., and L.S. designed research; V.H., J.A., and H.A.B. performed research; V.H., J.A., M.F., J.J.P., and A.N. contributed new reagents/analytic tools; V.H., J.A., H.A.B., J.J.P., A.N., and L.S. analyzed data; and V.H., J.A., and L.S. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: SUMO, small ubiquitin-like modifier; HSF, heat-shock factor; PDSM, phosphorylation-dependent sumoylation motif; MEF, myocyte-specific enhancer factor; ERR, estrogen-related receptor; SENP, SUMO/sentrin-specific protease.