1: Recent Prog Horm Res. 1997;52:103-19; discussion 119-20. 

The multifunctional role of the co-activator CBP in transcriptional regulation.

Goldman PS, Tran VK, Goodman RH.

Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.

One of the most studied and best-understood examples of second
messenger-regulated gene transcription involves the activation of genes by the
cyclic AMP pathway: stimulation of several hormone, growth factor, and
neurotransmitter receptors activates adenylyl cyclase, generating cyclic AMP
that, by binding to the regulatory subunit of protein kinase A (PKA),
dissociates the PKA catalytic subunit. The free catalytic subunit is transported
to the nucleus where it phosphorylates and consequently activates the
transcription factor CREB. This phosphorylation of CREB allows interaction with
the co-activator CBP, which binds to components of the basal transcriptional
machinery. CBP and its homologue p300 are targets for several viral-transforming
proteins, implying that these co-activators have a more extensive role in
cellular function. Indeed, recent studies have demonstrated that multiple
transcription factors bind to CBP, including c-jun, c-myb, MyoD, E2F1, YY1, and
members of the steroid hormone receptor superfamily, although it is not yet
clear which of these transcription factors depend upon CBP for function.
Determining exactly which transcriptional pathways require CBP in vivo and which
genes are activated by CBP will provide an important clue in developmental
regulation and cell cycle control, since mutations in the human CBP gene have
been found to cause developmental abnormalities and a predisposition for some
types of cancer. In this review, we will discuss the mechanisms involved in the
PKA-dependent activation of CREB and describe how the co-activator CBP and its
homologue are involved in this process. In addition, we will outline the various
transcription factor pathways that CBP has been proposed to activate. Finally,
we will discuss the possible role of CBP in cellular transformation and
differentiation.

Publication Types:
    Review

PMID: 9238849 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------