The proteins binding the cAMP responsive elements constitute a family of transcription factors (e.g. CREB 327/341, ATF, HB16, CREM) which operate as dimers and regulate positively and negatively gene expression upon interaction with the cAMP responsive motifs CRE/ATF. These proteins regulate transcription after cAMP- dependent phosphorylation (CREB), or interaction with the adenovirus E1A oncoprotein (ATF-2). Subtle modulation might be further attained by the cross-talk between the different signal-transduction pathways and the heterodimerization of different classes of transcription factors. The CREB/ATF transcription factors therefore exert a pleiotropic action during the integration of extra/intra cellular signals in the resulting adaptation of cellular responses. Dysregulation might be associated with pathological situations related to the uncontrolled cell proliferation, oncogenic progression and metastasis.

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