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Background
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The small
ubiquitin-related modifier (SUMO) proteins, which include SUMO-1, SUMO-2 and
SUMO-3, belong to the ubiquitin-like protein family. Like ubiquitin, the SUMO
proteins are synthesized as precursor proteins that undergo processing before
conjugation to target proteins. Also, both utilize the E1, E2, and E3 cascade
enzymes for conjugation. However, SUMO and ubiquitin differ with respect to
targeting. Ubiquitination predominantly targets proteins for degradation,
whereas sumoylation targets proteins to a variety of cellular processing,
including nuclear transport, transcriptional regulation, apoptosis and
protein stability. The unconjugated SUMO-1, SUMO-2 and SUMO-3 proteins
localize to the nuclear membrane, nuclear bodies and cytoplasm, respectively.
SUMO-1 utilizes Ubc9 for conjugation to several target proteins, which
include IkBa, MDM2, p53, PML and Ran GAP1. SUMO-2 and SUMO-3 contribute to a
greater percentage of protein modification than does SUMO-1, and unlike
SUMO-1, they can form polymeric chains. In addition, SUMO-3 regulates
b-Amyloid generation and may be critical in the onset or progression of
Alzheimer's disease.
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