CBP/p300 in cell growth, transformation, and development

  1. Richard H. Goodman1,3 and
  2. Sarah Smolik2
  1. 1Vollum Institute and 2Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201 USA

This extract was created in the absence of an abstract.

CREB binding protein (CBP) and p300 were both identified initially in protein interaction assays–the former through its association with the transcription factor CREB (Chrivia et al. 1993) and the latter through its interaction with the adenoviral-transforming protein E1A (Stein et al. 1990; Eckner et al. 1994). The recognition that these two proteins, one involved in transcription and the other in cell transformation, had highly conserved sequences suggested that they had the potential to participate in a variety of cellular functions (Fig.1). Several excellent reviews (Janknecht and Hunter 1996; Shikama et al. 1997; Giles et al. 1998) have addressed the transcriptional coactivator functions of CBP/p300; this review focuses on the involvement of these proteins in the complex biological processes that affect cell growth, transformation, and development.

Figure 1.

CBP/p300 organization and interactions. Interacting proteins are shown at the top of the figure; functional domains are depicted below. Many known interactions are not included due to space limitations.

Involvement of CBP/p300 in cell growth and transformation

CBP/p300 as tumor suppressors

One of the major paradoxes in CBP/p300 function is that these proteins appear to be capable of contributing to diametrically opposed cellular processes. This section begins with a review of the evidence that CBP and p300 participate in various tumor-suppressor pathways. It ends with the demonstration that these coactivators are essential for the actions of many oncogenes. Whether CBP and p300 promote apoptosis or cell proliferation appears to be highly context dependent.

Several characteristics of CBP and p300 suggested that these proteins might serve as tumor suppressors, but clear evidence for this function awaited the studies of Kung et al. (2000). Mice engineered to contain a null mutation in one CBP allele developed a variety of hematological abnormalities, including extramedullary myelopoiesis and erythropoiesis, lymph node hyperplasia, and splenomegaly. Most of these effects were attributed to an underlying bone marrow failure. As …

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