Reactome | SUMOylation of TFAP2A with SUMO1

SUMOylation of TFAP2A with SUMO1

Stable Identifier

R-HSA-3234081

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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
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
24835590	Sumoylation pathway is required to maintain the basal breast cancer subtype Li, T, Li, Y, Spanheimer, PM, Weigel, RJ, Park, JM, Kulak, MV, Bogachek, MV, Chen, Y, Cyr, AR, Woodfield, GW	Cancer Cell	2014
21375726	Alternative TFAP2A isoforms have distinct activities in breast cancer Berlato, C, Hurst, HC, Scibetta, AG, Chan, KV, Price, AM, Canosa, M	Breast Cancer Res.	2011
25114211	Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli Impens, F, Cossart, P, Radoshevich, L, Ribet, D	Proc. Natl. Acad. Sci. U.S.A.	2014

Participants

Input

Output

Participates

as an event of

Catalyst Activity

SUMO transferase activity of SUMO1:C93-UBE2I [nucleoplasm]

Physical Entity

SUMO1:C93-UBE2I [nucleoplasm] (Homo sapiens)

Activity

SUMO transferase activity (GO:0019789)

Inferred From

SUMOylation of TFAP2C with SUMO1 (Homo sapiens)

Authored

May, B (2013-03-27)

Reviewed

Zarelli, VE (2016-05-04)

Bogachek, MV (2016-05-17)

Dawid, IB (2016-05-04)

Weigel, RJ (2016-05-17)

Created

May, B (2013-03-27)