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

Full text not available from this repository.

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:	06 Jan 2024 03:57
URI:	https://orca.cardiff.ac.uk/id/eprint/332

Citation Data

Cited 44 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item