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SUMOylation is a reversible post-translational modification in
which small ubiquitin-like modifier proteins (SUMO1, SUMO2 and SUMO3)
are covalently attached to target proteins. The pathway uses the SUMO E1
activating complex SAE1/UBA2, the E2 conjugating enzyme
UBE2I/UBC9 and various E3 SUMO ligases, including members of
the PIAS family. SUMOylation regulates protein stability, localization,
transcription, chromatin structure, DNA-damage repair, cell-cycle progression
and cellular stress responses. The SUMO pathway is frequently increased or
dysregulated in cancer and can support proliferation, DNA repair, oncogenic
signalling, invasion, metastasis and resistance to cellular stress or anticancer
therapy. Consequently, the typical cancer-associated direction is generally
up, while the desired anticancer modulation is commonly
down or inhibition of SUMO conjugation. However, effects are
substrate-dependent because SUMOylation of individual proteins can have either
tumour-promoting or tumour-suppressive consequences. SUMOylation is an umbrella pathway target, with SAE1, UBA2, UBE2I/UBC9,SUMO1/2/3 and specific SUMO-modified proteins recorded separately when identified.
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