| First Author | Schmidt D | Year | 2008 |
| Journal | Exp Cell Res | Volume | 314 |
| Issue | 20 | Pages | 3614-27 |
| PubMed ID | 18845144 | Mgi Jnum | J:143410 |
| Mgi Id | MGI:3826899 | Doi | 10.1016/j.yexcr.2008.09.008 |
| Citation | Schmidt D, et al. (2008) Blimp-1Deltaexon7: a naturally occurring Blimp-1 deletion mutant with auto-regulatory potential. Exp Cell Res 314(20):3614-27 |
| abstractText | Blimp-1 is a master regulator of terminal B cell differentiation and plays a pivotal role in various developmental processes. In addition to full length Blimp-1, a Blimp-1 mRNA lacking exon 7 (Blimp-1Delta7) has been described to occur in murine B cells. The activity and function of the mutant mRNA-encoded protein (Blimp-1Delta7), lacking three crucial zinc fingers necessary for DNA interaction, is completely unknown. Since isoforms of other prdm family proteins affect each other's functions, we wondered whether Blimp-1Delta7 still plays a role in B cells, independent of direct DNA binding. In this study, we found that Blimp-1Delta7 is preferentially expressed in naive CD19(+) B cells. A fraction of Blimp-1Delta7 migrates to the nucleus, colocalizes with HDAC2 and is found at sites of repressed chromatin, although it does not bind to the Blimp-1 DNA consensus site. Unexpectedly, Blimp-1 and Blimp-1Delta7 homodimerize as well as heterodimerize with each other. Ectopic expression of Blimp-1Delta7 in WEHI 231 cells, a Blimp-1-negative murine lymphoma line, leads to cessation of proliferation and enhancement of apoptosis. Importantly, LPS-induced differentiation is suppressed in the presence of Blimp-1Delta7. This is in agreement with our finding that Blimp-1Delta7 interferes with endogenous Blimp-1 expression. Thus, our data suggest an auto-regulatory mechanism of Blimp-1 activation. |
