CDKN1A gene expression is stimulated by TFAP2A and repressed by TFAP2C

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Reaction [omitted]
Homo sapiens
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The CDKN1A gene encodes cyclin dependent kinase inhibitor also known as p21 or WAF1 which can induce G1 cell cycle arrest.

Binding of TFAP2A (AP-2 alpha) transcription factor to the CDKN1A promoter results in the activation of CDKN1A expression in a TP53 (p53) independent manner, which may be important during development and differentiation (Zeng et al. 1997, Williams et al. 2009, Scibetta et al. 2010).

Binding of TFAP2C (AP-2 gamma) transcription factor to the proximal AP-2 response element in the CDKN1A promoter (Scibetta et al. 2010) results in repression of CDKN1A transcription. TFAP2C may recruit histone deacetylases, such as HDAC2 to the CDKN1A promoter (Williams et al. 2009). TFAP2C cooperates with its interaction partners MYC and KDM5B in repression of the CDKN1A gene transcription. The mechanism may involve KDM5B-mediated removal of activating histone methylation mark at H3K4 from nucleosomes at the CDKN1A promoter. In the absence of TFAP2C, MYC can recruit KDM5B to the CDKN1A promoter via an AP-2 independent MYC-binding site, but this results in a lower level of CDKN1A gene repression. TFAP2C-mediated repression of CDKN1A transcription promotes G1/S transition (Wong et al. 2012). In contradiction, it has been reported that TFAP2C may induce, instead of repress CDKN1A transcription (Li et al. 2006).

Literature References
PubMed ID Title Journal Year
8988173 AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression

el-Deiry, WS, Zeng, YX, Somasundaram, K

Nat. Genet. 1997
22371483 Histone demethylase KDM5B collaborates with TFAP2C and Myc to repress the cell cycle inhibitor p21(cip) (CDKN1A)

Berlato, C, Hurst, HC, Miranda, F, Wong, PP, Scibetta, AG, Chan, KV

Mol. Cell. Biol. 2012
19798054 AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene

Berlato, C, Moss, CH, Hurst, HC, Scibetta, AG, Friedrich, JK, Williams, CM, Canosa, M

EMBO J. 2009
21084835 Dual association by TFAP2A during activation of the p21cip/CDKN1A promoter

Hurst, HC, Wong, PP, Scibetta, AG, Chan, KV, Canosa, M

Cell Cycle 2010
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