Abstract
We have demonstrated previously that DNA binding and protein expression of the E2A-encoded transcription factor E47 are lower in nuclear extracts of activated splenic B cells from old mice. In the present study, we address how E47 protein expression is regulated in aging. Results herein show that E2A mRNA levels were decreased in stimulated splenic B cells from old as compared with young mice. RNA stability assays showed that the rate of E2A mRNA decay was accelerated in stimulated splenic B cells from old mice, but E47 protein degradation rates were comparable in young vs aged B cells, indicating that the regulation of E47 expression in activated splenic B cells occurs primarily by mRNA stability. The rates of decay of other mRNAs showed that the increased mRNA degradation in aged splenic activated B cells is not a general phenomenon but restricted to a subset of mRNAs. We next investigated the signal transduction pathways controlling E2A mRNA expression and stability and found that p38 MAPK regulates E2A mRNA expression through increased mRNA stability and is down-regulated in aged activated B cells. Results show that inhibition of p38 MAPK significantly reduces E2A mMNA stability in both young and old B cells, further stressing the role of p38 MAPK in E2A MNA stabilization. These studies demonstrate that the transcription factor E2A, critical for many aspects of B cell function, is regulated by a novel mechanism in aging.
| Original language | English |
|---|---|
| Pages (from-to) | 6633-6644 |
| Number of pages | 12 |
| Journal | Journal of Immunology |
| Volume | 175 |
| Issue number | 10 |
| State | Published - Nov 15 2005 |
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ASJC Scopus subject areas
- Immunology
Cite this
RNA stability of the E2A-encoded transcription factor E47 is lower in splenic activated B cel ls from aged mice. / Frasca, Daniela; Van der Put, Elaine; Landin, Ana Marie; Gong, Dapeng; Riley, Richard L; Blomberg, Bonnie B.
In: Journal of Immunology, Vol. 175, No. 10, 15.11.2005, p. 6633-6644.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RNA stability of the E2A-encoded transcription factor E47 is lower in splenic activated B cel ls from aged mice
AU - Frasca, Daniela
AU - Van der Put, Elaine
AU - Landin, Ana Marie
AU - Gong, Dapeng
AU - Riley, Richard L
AU - Blomberg, Bonnie B
PY - 2005/11/15
Y1 - 2005/11/15
N2 - We have demonstrated previously that DNA binding and protein expression of the E2A-encoded transcription factor E47 are lower in nuclear extracts of activated splenic B cells from old mice. In the present study, we address how E47 protein expression is regulated in aging. Results herein show that E2A mRNA levels were decreased in stimulated splenic B cells from old as compared with young mice. RNA stability assays showed that the rate of E2A mRNA decay was accelerated in stimulated splenic B cells from old mice, but E47 protein degradation rates were comparable in young vs aged B cells, indicating that the regulation of E47 expression in activated splenic B cells occurs primarily by mRNA stability. The rates of decay of other mRNAs showed that the increased mRNA degradation in aged splenic activated B cells is not a general phenomenon but restricted to a subset of mRNAs. We next investigated the signal transduction pathways controlling E2A mRNA expression and stability and found that p38 MAPK regulates E2A mRNA expression through increased mRNA stability and is down-regulated in aged activated B cells. Results show that inhibition of p38 MAPK significantly reduces E2A mMNA stability in both young and old B cells, further stressing the role of p38 MAPK in E2A MNA stabilization. These studies demonstrate that the transcription factor E2A, critical for many aspects of B cell function, is regulated by a novel mechanism in aging.
AB - We have demonstrated previously that DNA binding and protein expression of the E2A-encoded transcription factor E47 are lower in nuclear extracts of activated splenic B cells from old mice. In the present study, we address how E47 protein expression is regulated in aging. Results herein show that E2A mRNA levels were decreased in stimulated splenic B cells from old as compared with young mice. RNA stability assays showed that the rate of E2A mRNA decay was accelerated in stimulated splenic B cells from old mice, but E47 protein degradation rates were comparable in young vs aged B cells, indicating that the regulation of E47 expression in activated splenic B cells occurs primarily by mRNA stability. The rates of decay of other mRNAs showed that the increased mRNA degradation in aged splenic activated B cells is not a general phenomenon but restricted to a subset of mRNAs. We next investigated the signal transduction pathways controlling E2A mRNA expression and stability and found that p38 MAPK regulates E2A mRNA expression through increased mRNA stability and is down-regulated in aged activated B cells. Results show that inhibition of p38 MAPK significantly reduces E2A mMNA stability in both young and old B cells, further stressing the role of p38 MAPK in E2A MNA stabilization. These studies demonstrate that the transcription factor E2A, critical for many aspects of B cell function, is regulated by a novel mechanism in aging.
UR - http://www.scopus.com/inward/record.url?scp=27744483838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744483838&partnerID=8YFLogxK
M3 - Article
C2 - 16272318
AN - SCOPUS:27744483838
VL - 175
SP - 6633
EP - 6644
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -