Abstract
The transcription factor E47, which regulates immunoglobulin class switch in murine splenic B cells, is down-regulated in aged B cells due to reduced mRNA stability. Part of the decreased stability of E47 mRNA is mediated by tristetraprolin (TTP), a physiological regulator of mRNA stability. We have previously shown that TTP mRNA and protein expression are higher in old B cells, and the protein is less phosphorylated in old B cells, both of which lead to more binding of TTP to the 3'-UTR of E47 mRNA, thereby decreasing its stability. PP2A is a protein phosphatase that plays an important role in the regulation of a number of major signaling pathways. Herein we show that not only the amount but also the activity of PP2A is increased in old B cells. As a consequence of this higher phosphatase activity in old B cells, p38 MAPK and TTP (either directly or indirectly by PP2A) are less phosphorylated as compared with young B cells. PP2A dephosphorylation of p38 MAPK and/or TTP likely generates more binding of the hypophosphorylated TTP to the E47 mRNA, inducing its degradation. This mechanism may be at least in part responsible for the age-related decrease in class switch.
| Original language | English |
|---|---|
| Pages (from-to) | 306-314 |
| Number of pages | 9 |
| Journal | Mechanisms of Ageing and Development |
| Volume | 131 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2010 |
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Keywords
- Aging
- B cells
- Immunoglobulin (Ig) class switch
- Phosphatase (PP2A) activity
ASJC Scopus subject areas
- Aging
- Developmental Biology
Cite this
Protein phosphatase 2A (PP2A) is increased in old murine B cells and mediates p38 MAPK/tristetraprolin dephosphorylation and E47 mRNA instability. / Frasca, Daniela; Romero, Maria; Landin, Ana Marie; Diaz, Alain; Riley, Richard L; Blomberg, Bonnie B.
In: Mechanisms of Ageing and Development, Vol. 131, No. 5, 01.05.2010, p. 306-314.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protein phosphatase 2A (PP2A) is increased in old murine B cells and mediates p38 MAPK/tristetraprolin dephosphorylation and E47 mRNA instability
AU - Frasca, Daniela
AU - Romero, Maria
AU - Landin, Ana Marie
AU - Diaz, Alain
AU - Riley, Richard L
AU - Blomberg, Bonnie B
PY - 2010/5/1
Y1 - 2010/5/1
N2 - The transcription factor E47, which regulates immunoglobulin class switch in murine splenic B cells, is down-regulated in aged B cells due to reduced mRNA stability. Part of the decreased stability of E47 mRNA is mediated by tristetraprolin (TTP), a physiological regulator of mRNA stability. We have previously shown that TTP mRNA and protein expression are higher in old B cells, and the protein is less phosphorylated in old B cells, both of which lead to more binding of TTP to the 3'-UTR of E47 mRNA, thereby decreasing its stability. PP2A is a protein phosphatase that plays an important role in the regulation of a number of major signaling pathways. Herein we show that not only the amount but also the activity of PP2A is increased in old B cells. As a consequence of this higher phosphatase activity in old B cells, p38 MAPK and TTP (either directly or indirectly by PP2A) are less phosphorylated as compared with young B cells. PP2A dephosphorylation of p38 MAPK and/or TTP likely generates more binding of the hypophosphorylated TTP to the E47 mRNA, inducing its degradation. This mechanism may be at least in part responsible for the age-related decrease in class switch.
AB - The transcription factor E47, which regulates immunoglobulin class switch in murine splenic B cells, is down-regulated in aged B cells due to reduced mRNA stability. Part of the decreased stability of E47 mRNA is mediated by tristetraprolin (TTP), a physiological regulator of mRNA stability. We have previously shown that TTP mRNA and protein expression are higher in old B cells, and the protein is less phosphorylated in old B cells, both of which lead to more binding of TTP to the 3'-UTR of E47 mRNA, thereby decreasing its stability. PP2A is a protein phosphatase that plays an important role in the regulation of a number of major signaling pathways. Herein we show that not only the amount but also the activity of PP2A is increased in old B cells. As a consequence of this higher phosphatase activity in old B cells, p38 MAPK and TTP (either directly or indirectly by PP2A) are less phosphorylated as compared with young B cells. PP2A dephosphorylation of p38 MAPK and/or TTP likely generates more binding of the hypophosphorylated TTP to the E47 mRNA, inducing its degradation. This mechanism may be at least in part responsible for the age-related decrease in class switch.
KW - Aging
KW - B cells
KW - Immunoglobulin (Ig) class switch
KW - Phosphatase (PP2A) activity
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UR - http://www.scopus.com/inward/citedby.url?scp=77953050555&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2010.02.002
DO - 10.1016/j.mad.2010.02.002
M3 - Article
VL - 131
SP - 306
EP - 314
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
IS - 5
ER -