P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity.

P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Research Abstract Details 

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P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Abstract Text:

Lili Zhang,Linghu Nie,Carl G Maki,

BACKGROUND: p53 is a tumor suppressor and potent inhibitor of cell growth. P73 is highly similar to p53 at both the amino acid sequence and structural levels. Given their similarities, it is important to determine whether p53 and p73 function in similar or distinct pathways. There is abundant evidence for negative cross-talk between glucocorticoid receptor (GR) and p53. Neither physical nor functional interactions between GR and p73 have been reported. In this study, we examined the ability of p53 and p73 to interact with and inhibit GR transcriptional activity. RESULTS: We show that both p53 and p73 can bind GR, and that p53 and p73-mediated transcriptional activity is inhibited by GR co-expression. Wild-type p53 efficiently inhibited GR transcriptional activity in cells expressing both proteins. Surprisingly, however, p73 was either unable to efficiently inhibit GR, or increased GR activity slightly. To examine the basis for this difference, a series of p53:p73 chimeric proteins were generated in which corresponding regions of either protein have been swapped. Replacing N- and C-terminal sequences in p53 with the corresponding sequences from p73 prevented it from inhibiting GR. In contrast, replacing p73 N- and C-terminal sequences with the corresponding sequences from p53 allowed it to efficiently inhibit GR. Differences in GR inhibition were not related to differences in transcriptional activity of the p53:p73 chimeras or their ability to bind GR. CONCLUSION: Our results indicate that both N- and C-terminal regions of p53 and p73 contribute to their regulation of GR. The differential ability of p53 and p73 to inhibit GR is due, in part, to differences in their N-terminal and C-terminal sequences.

P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Publishing Authors By Initials

L Zhang,L Nie,CG Maki,

For similar proteins: neoplasm proteins: tumor suppressor proteins research abstracts see: proteins: neoplasm proteins: tumor suppressor proteins research

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P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular cancer

VOLUME: 5

Page Numbers: 68

Journal Abbreviation: Mol. Cancer

ISSN: 1476-4598

DAY: 6

MONTH: 12

YEAR: 2006

P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101147698

P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity. Information

Substance Name: Proto-Oncogene Proteins c-mdm2

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity.

AFFILIATION: Institute of Medicinal Biotechnology, Peking Union Medical College, Beijing, China. zhanglili623@gmail.com

Country: England

AGENCY: United States NCI

GRANT: 1R01 CA108843-02

ACRONYM: CA

MEDLINETA: Mol Cancer

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