SUMOylation of TFAP2A with SUMO1

Stable Identifier
R-HSA-3234081
Type
Reaction [transition]
Species
Homo sapiens
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UBE2I (UBC9) interacts with TFAP2A, TFAP2B and TFAP2C, and the interaction site has been mapped to the C terminal region of TFAP2C; SUMOylation occurs on lysine-10 (Eloranta and Hurst 2002). As lysine-10 is conserved in TFAP2A and TFAP2B, SUMOylation of these factors is assumed to be on lysine-10 (Eloranta and Hurst 2002; Impens et al. 2014). SUMOylation causes a reduction in AP-2 transcriptional activation function but is required for its repressive function. A dominant negative mutant of UBC9 led to increased activation and reduced repressor function of TFAP2A and C, supporting the role of UBC9 in SUMOylation (Eloranta and Hurst 2002; Berlato et al. 2011). Isoform 1a of TFAP2A is SUMOylated, isoforms 1b and 1c lack lysine 10 and are not SUMOylated (Berlato et al. 2011). TFAP2D and TFAP2E lack lysine-10 and are thus assumed not to be SUMOylated. SUMOylation of TFAP2A blocked its ability to induce the expression of luminal genes and repression of basal genes (Bogachek et al. 2014). Disruption of the sumoylation pathway by knockdown of sumoylation enzymes, mutation of the SUMO-target lysine of TFAP2A, or treatment with sumoylation inhibitors induced MET in basal breast cancers, which was dependent on TFAP2A(Bogachek et al. 2014).

Literature References
PubMed ID Title Journal Year
24835590 Sumoylation pathway is required to maintain the basal breast cancer subtype

Bogachek, MV, Chen, Y, Kulak, MV, Woodfield, GW, Cyr, AR, Park, JM, Spanheimer, PM, Li, Y, Li, T, Weigel, RJ

Cancer Cell 2014
12072434 Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo

Eloranta, JJ, Hurst, HC

J. Biol. Chem. 2002
21375726 Alternative TFAP2A isoforms have distinct activities in breast cancer

Berlato, C, Chan, KV, Price, AM, Canosa, M, Scibetta, AG, Hurst, HC

Breast Cancer Res. 2011
25114211 Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli

Impens, F, Radoshevich, L, Cossart, P, Ribet, D

Proc. Natl. Acad. Sci. U.S.A. 2014
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Catalyst Activity
Title
SUMO transferase activity of SUMO1:C93-UBE2I [nucleoplasm]
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