Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB in lymphocytes

White, Paul Charles ORCID: https://orcid.org/0000-0002-6562-4696, Shore, A. M., Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, McLaren, James Edward ORCID: https://orcid.org/0000-0002-7021-5934, Soeiro, I., Lam, E. W.-F. and Brennan, Paul ORCID: https://orcid.org/0000-0001-8792-0499 2006. Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB in lymphocytes. Oncogene 25 (15) , pp. 2170-2180. 10.1038/sj.onc.1209255

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Abstract

Lymphocyte proliferation is key to the regulation of the immune system. Cyclin D2 is the first cell cycle protein induced following stimulation through the T-cell receptor, the B-cell receptor or cytokines. The promoter of this cyclin integrates a diverse range of signals. Through investigating the regulation of this promoter by interleukin-2 and phosphatidylinositol 3-kinase, we have identified a role for the transcription factor CREB, cAMP response element-binding protein. Mutation of the CREB-binding site reduced cyclin D2 promoter activity 5–10-fold. CREB-1 is phosphorylated at serine 133, a critical site for activity, in both T cells and Epstein–Barr virus immortalized B cells. The introduction of an S133A mutant of CREB-1 reduces IL-2 induction of cyclin D2 promoter activity, demonstrating a role for this phosphorylation site in promoter activity. Two inhibitors of protein kinase A reduce lymphocyte proliferation and CREB-1 phosphorylation. This study demonstrates that the cyclin D2 promoter is capable of being regulated by PI3K and CREB and identifies CREB-1 and protein kinase A as potential targets for altering lymphocyte proliferation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	cyclin D2 ; phosphatidylinositol 3-kinase ; CREB ; interelukin-2 ; Epstein–Barr virus
ISSN:	0950-9232
Last Modified:	01 Nov 2024 17:02
URI:	https://orca.cardiff.ac.uk/id/eprint/332

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