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CD74 induces TAp63 expression leading to B-cell survival.
- Source :
-
Blood [Blood] 2007 Dec 15; Vol. 110 (13), pp. 4303-11. Date of Electronic Publication: 2007 Sep 10. - Publication Year :
- 2007
-
Abstract
- Most mature follicular B cells circulate within the periphery in a quiescent state, without actively contributing to an acute immune response. Lasting B-cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. We recently demonstrated that cell surface CD74 controls mature B-cell survival. Stimulation of cell surface CD74 leads to NF-kappaB activation, which enables entry of the stimulated B cells into the S phase, induction of DNA synthesis, and cell division, and augments the expression of survival genes. In the present study, we investigated CD74 target genes to determine the identities of the molecules whose expression is modulated by CD74, thereby regulating B-cell survival. We report that CD74 activates the p65 member of the NF-kappaB family, which in turn up-regulates the expression of p53-related TAp63 proteins. TAp63 then binds and transactivates the Bcl-2gene and induces the production of Bcl-2 protein, thereby providing the cells with increased survival capacity. Thus, the CD74/NF-kappaB/TAp63 axis defines a novel antiapoptotic pathway in mature B cells, resulting in the shaping of both the B-cell repertoire and the immune response.
- Subjects :
- Active Transport, Cell Nucleus
Animals
Cell Survival
Mice
Mice, Knockout
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Proto-Oncogene Proteins c-bcl-2 genetics
Trans-Activators genetics
Transcription, Genetic
Up-Regulation
Antigens, Differentiation, B-Lymphocyte physiology
B-Lymphocytes cytology
Histocompatibility Antigens Class II physiology
Phosphoproteins physiology
Trans-Activators physiology
Transcription Factor RelA metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 110
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 17846227
- Full Text :
- https://doi.org/10.1182/blood-2007-04-087486