Dataset Information

A p38 MAPK-MEF2C pathway regulates B-cell proliferation.

ABSTRACT: B lymphocytes are an integral part of the adaptive immune system. On antigen binding to the B-cell receptor (BCR), B cells rapidly proliferate and differentiate into antibody-secreting plasma cells. The p38 mitogen-activated protein kinase (MAPK) pathway functions downstream of the BCR to control cell proliferation, but the transcriptional effectors of this pathway in B cells have remained elusive. In the present study, we inactivated Mef2c exclusively in B cells by conditional gene targeting in mice. Loss of MEF2C function resulted in a reduced immune response to antigen, defective germinal center formation, and a severe defect in B-cell proliferation, and we show that MEF2C regulates proliferation in response to BCR stimulation via the p38 MAPK pathway. p38 directly phosphorylates MEF2C via three residues in the C-terminal transactivation domain, establishing MEF2C as a direct transcriptional effector of BCR signaling via p38 MAPK.

SUBMITTER: Khiem D

PROVIDER: S-EPMC2579379 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A p38 MAPK-MEF2C pathway regulates B-cell proliferation.

Khiem Dustin D Cyster Jason G JG Schwarz John J JJ Black Brian L BL

Proceedings of the National Academy of Sciences of the United States of America 20081027 44

B lymphocytes are an integral part of the adaptive immune system. On antigen binding to the B-cell receptor (BCR), B cells rapidly proliferate and differentiate into antibody-secreting plasma cells. The p38 mitogen-activated protein kinase (MAPK) pathway functions downstream of the BCR to control cell proliferation, but the transcriptional effectors of this pathway in B cells have remained elusive. In the present study, we inactivated Mef2c exclusively in B cells by conditional gene targeting in ...[more]

PMID: 18955699

Similar Datasets

Project description:Laryngeal carcinoma (LCC) is a common malignant tumor with low radiosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n‑recognin 5 (UBR5) has prognostic implications in several neoplasms; however, its role in LCC and radiotherapy sensitivity remains unknown. Immunohistochemistry and bioinformatics analyses were performed to measure UBR5 protein and mRNA expression in LCC and adjacent non‑tumor tissues. The gene and protein expression of UBR5 in LCC and HuLa‑PC cell lines were measured using quantitative PCR and western blot analyses. Following transfection with small interfering RNA or UBR5 overexpression plasmid in LCC cells, the proliferation, cell cycle distribution, invasion, migration and radiosensitivity of LCC cells were analyzed. UBR5‑related lncRNA, targeted miRNA and protein‑protein interaction networks were analyzed using bioinformatics. Finally, the expression of the p38/mitogen‑activated protein kinase (MAPK) pathway was evaluated following UBR5 silencing in M2E cells treated with radiation. Increased UBR5 expression was observed in LCC tissues compared with adjacent non‑tumor tissues, and it was correlated with poor overall survival of LCC patients. After overexpression or silencing of UBR5 in M2E and M4E LCC cells, cell proliferation and radiosensitivity were significantly increased or decreased, respectively, compared with the control groups. The percentage of S phase cells decreased in the UBR5 si‑RNA group compared with that in the control group, while overexpression of UBR5 exerted no effect on the cell cycle. In addition, the expression of Bcl‑2 and p38 was decreased in the si‑UBR5 combined with radiation groups. The level of phosphorylated p38 expression was increased after combination of si‑UBR5 with radiation. The small molecule inhibitor of p38/MAPK signaling, SB203580, decreased the viability of UBR5‑overexpressing cells and the survival fraction when cells were exposed to radiation. These findings demonstrated that UBR5 may be involved in regulating cell proliferation and sensitivity to radiotherapy in LCC via the p38/MAPK pathway, thereby highlighting its possible value for the development of new therapeutic strategies and targets for the treatment of this disease.

Dataset Information

A p38 MAPK-MEF2C pathway regulates B-cell proliferation.

Publications

A p38 MAPK-MEF2C pathway regulates B-cell proliferation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets