Inefficient proteasomal-degradation pathway stabilizes AP-2alpha and activates HER-2/neu gene in breast cancer.

HER-2/neu proto-oncogene is overexpressed in about one fourth of human breast cancers. AP-2 transcription factors bind to the HER-2/neu gene promoter and activate its expression. In a striking concurrence, anomalous abundance of AP-2alpha protein or its homolog AP-2gamma is also detected with HER-2/neu protein in mammary tumor-derived cell lines.

Dual regulation of AP-2alpha transcriptional activation by poly(ADP-ribose) polymerase-1.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a co-activator for AP-2alpha (activator protein 2alpha)-mediated transcriptional activation. In the present study, we find that the role of PARP-1 in AP-2alpha transcription is distinctly dualistic with opposing effects. Separate regions of PARP-1 interact with AP-2alpha and independently control its transcriptional activation.

Functional characterization of the interacting domains of the positive coactivator PC4 with the transcription factor AP-2alpha.

The transcriptional positive cofactor 4 (PC4) physically interacts with the transcription factor, activator protein-2 (AP-2) alpha, and overexpression of PC4 results in a relief of the AP-2 transcriptional self-interference, which is induced by high levels of AP-2alpha expression. PC4 was initially described as a DNA-binding protein that enhances the activator-dependent transcription of class II genes in vitro, but it was later shown that PC4 could also act as a potent repressor of transcription on specific DNA structures such as single-stranded (ss) DNA, DNA ends and heteroduplex DNA. To further explore the functional domains of PC4 and its ssDNA-binding effect in the interaction with AP-2alpha and on AP-2 transcriptional activity, we investigated the C-terminal domain of PC4 (PC4-CTD) and several PC4 mutants in which the ssDNA binding function was interrupted.

The human transcription factor activation protein-2 gamma (AP-2gamma): gene structure, promoter, and expression in mammary carcinoma cell lines.

Human activation protein-2 gamma (hAP-2gamma) is a key developmental transcription factor. It has been implicated in mammary carcinogenesis through its regulation of HER-2/neu proto-oncogene and estrogen receptor gene The hAP-2gamma gene is located on human chromosome 20q13.2.

Tumorigenic effect of transcription factor hAP-2alpha and the intricate link between hAP-2alpha activation and squelching.

Overexpression of human activator protein-2alpha (hAP-2alpha) is carcinogenic. Its aberrant regulation is the underlying tumorigenic event in the human teratocarcinoma cell line PA-1. In this cell line excess hAP-2alpha protein binds and sequesters coactivators, which interferes with the activity of other activators and with its own activity.