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Are: Transformation Related Protein 53 A Tumor Suppressor

The recognition that these two proteins, one involved in transcription and the other in Protrin transformation, had highly conserved sequences suggested that they had the potential to participate in a variety of cellular functions Fig. Several excellent reviews Janknecht and Hunter ; Shikama et al. Interacting proteins are shown at the top of the figure; functional domains are depicted below.

Original Research ARTICLE

Many known interactions are not included due Transformation Related Protein 53 A Tumor Suppressor space limitations. This section begins with a review of the evidence that CBP and p 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 p promote apoptosis or cell proliferation appears to be highly context dependent.

Several characteristics of CBP and p RRelated that these proteins might Tmuor as tumor suppressors, but clear evidence for this function awaited the studies of Kung et al. 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 the mutant animals aged, they developed a strikingly high incidence of hematological malignancies, including histiocytic sarcomas, monomyelocytic leukemia, and lymphocytic leukemia.

More aggressive forms of leukemia developed in sublethally irradiated recipients transplanted with bone marrow or splenocytes from the CBP heterozygotes.

UBC Theses and Dissertations

Analysis of tumors isolated from the irradiated recipients revealed that the wild-type CBP allele was Trajsformation lost as well. This loss of heterozygosity in a population of cells that undergoes transformation is a hallmark feature of a tumor-suppressor gene. Surprisingly, the hematological defects and cancer predisposition were not seen in mice that contained the identical mutation in one p allele.

However, a tumor-suppressor role for p in humans is not inconceivable. Muroaka et al. The growth suppression functions of CBP and p are also Transforamtion by their interactions with the tumor suppressor p Most of the here functions of p53 are believed to occur through its ability to activate genes involved in the response to DNA damage, such as murine double minute mdm-2p21, cyclin G, and bax. Conversely, the growth suppression activities of CBP and p have been attributed to their ability to augment pmediated transcription. In addition to its transcriptional activation functions, p53 negatively regulates genes whose promoters do not contain a suitable Transformation Related Protein 53 A Tumor Suppressor site.

Avanaggiati et al. A pinteracting factor called JMY has been identified and proposed to augment pdependent apoptosis Shikama et al.

Nanomaterial-Based PTT for Tumor Treatment

Acetylation of specific lysine residues in the carboxyl terminus of p53 was found to increase DNA binding dramatically, presumably by altering the conformation of an inhibitory regulatory domain. One model for how this might occur is that the neutralization of positively charged lysine residues through acetylation might disrupt interactions between the p53 carboxyl terminus and the core DNA-binding domain. The ability of p53 to be acetylated uSppressor vivo was confirmed subsequently by using acetylation-specific antibodies Sakaguchi et al.

Lambert et al.

Amino-terminal phosphorylation also decreases the affinity of p53 for mdm-2 Chehab et al. The correlation between histone acetylation and gene activation has been reviewed extensively for example, see Strahl and Allis The studies of Gu and Roeder provided the first demonstration that acetylation can regulate the transcriptional functions of non-histone proteins link well. However, in most instances, precisely how acetylation affects the transcriptional properties of these other proteins is not completely understood.

For example, the p53 protein is known to be stabilized in cells that express adenovirus E1A. As described above, E1A blocks the ability of p53 to induce its target genes, such as mdm2. Because mdm2 is implicated in p53 degradation Haupt et al. Grossman et al.]