Preferred Label : Sumoylation Pathway;
NCIt related terms : Basic Mechanisms of SUMOylation;
Alternative definition : BIOCARTA: Like ubiquitin, SUMO (small ubiquitin-related modifier) proteins are small
protein tags that are conjugated to proteins to modify their function. The ubiquitin
system tags proteins for degradation by the proteasome but SUMO conjugation has a
range of other functions, stabilizing some proteins and altering their subcellular
localization. Sumoylation may also influence ubiquitination and protein stability
indirectly. Three different SUMO proteins are conjugated to proteins, SUMO-1, SUMO-2
and SUMO-3. The SUMO-2 and SUMO-3 genes are closely related, with 86% sequence identity
while SUMO-1 is less closely related with about 50% sequence identity with SUMO-2
and SUMO-3. These SUMO proteins also have distinct functions, with SUMO-1 conjugated
to proteins as a monomer, while SUMO-2 and SUMO-3 are conjugated to proteins as higher
molecular weight polymers with SUMO-1 terminating further SUMO addition. SUMO proteins
are first activated by adenylation by one enzyme complex (SAE1/SAE2), then transferred
to Ubc-9 and finally to the terminal amino group of a lysine side chain in target
proteins. The same conjugation system appears to work for all three SUMO proteins.
One target of SUMO modification is proteins involved in formation of the PML nuclear
bodies, promoting the stability of these structures and perhaps altering their role
in transcriptional regulation, cellular proliferation and anti-viral responses. Other
targets of SUMO addition include DAXX, p53 and ran-Gap. The transcriptional activation
by p53 is increased by SUMO addition. The localization of DAXX to the PML nuclear
bodies and the localization of ran-Gap to the nuclear pores are also regulated by
SUMO addition. The activity of several transcription factors is altered by sumoylation,
including C/EBP proteins, c-Myb, glucocorticoid receptor, androgen receptor, and progesterone
receptor. PIAS is a protein that modulates the activity of many different transcription
factors perhaps by acting itself as a sumo ligase. Sumoylation of topoisomerase I
alters its localization in the nucleus, and histone deacetylase enzymes are targets
of this system. Viral proteins are targets of sumoylation, suggesting that infection
and anti-viral cellular defenses may be affected by this system. Sumoylation may also
alter the stability of proteins with polyglutamine repeats involved in neurodegenerative
disorders, adding further to the important and diverse roles of this protein modification
system. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_sumoPathway;
Origin ID : C39242;
UMLS CUI : C1515052;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
