Abstract
The CCAAT/enhancer binding protein α (C/EBPα) and CCAAT/enhancer binding protein β (C/EBPβ) mRNAs are templates for the differential translation of several isoforms. Immunoblotting detects C/EBPαs with molecular masses of 42, 38, 30, and 20 kDa and C/EBPβs of 35, 20, and ~8.5 kDa. The DNA-binding activities and pool levels of p42(C/EBPα) and p30(C/EBPα) in control nuclear extracts decrease significantly whereas the binding activity and protein levels of the 20-kDa isoforms increase dramatically with LPS treatment. Our studies suggest that the LPS response involves alternative translational initiation at specific in-frame AUGs, producing specific C/EBPα and C/EBPβ isoform patterns. We propose that alternative translational initiation occurs by a leaky ribosomal scanning mechanism. We find that nuclear extracts from normal aged mouse livers have decreased p42(C/EBPα) levels and binding activity, whereas those of p20(C/EBPα) and p20(C/ESPβ) are increased. However, translation of 42-kDa C/EBPα is not down-regulated on polysomes, suggesting that aging may affect its nuclear translocation. Furthermore, recovery of the C/EBPα- and C/EBPβ- binding activities and pool levels from an LPS challenge is delayed significantly in aged mouse livers. Thus, aged livers have altered steady- state levels of C/EBPα and C/EBPβ isoforms. This result suggests that normal aging liver exhibits characteristics of chronic stress and a severe inability to recover from an inflammatory challenge.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1479-1494 |
| Number of pages | 16 |
| Journal | Molecular Biology of the Cell |
| Volume | 9 |
| Issue number | 6 |
| State | Published - Jun 1998 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
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Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding protein α and CCAAT/enhancer binding protein β isoform synthesis in control and LPS-treated livers. / Hsieh, Ching Chyuan; Xiong, Wei; Xie, Qizhi; Rabek, Jeffrey P.; Scott, Sheen G.; An, Mi Ra; Reisner, Peter D.; Kuninger, David T.; Papaconstantinou, John.
In: Molecular Biology of the Cell, Vol. 9, No. 6, 06.1998, p. 1479-1494.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding protein α and CCAAT/enhancer binding protein β isoform synthesis in control and LPS-treated livers
AU - Hsieh, Ching Chyuan
AU - Xiong, Wei
AU - Xie, Qizhi
AU - Rabek, Jeffrey P.
AU - Scott, Sheen G.
AU - An, Mi Ra
AU - Reisner, Peter D.
AU - Kuninger, David T.
AU - Papaconstantinou, John
PY - 1998/6
Y1 - 1998/6
N2 - The CCAAT/enhancer binding protein α (C/EBPα) and CCAAT/enhancer binding protein β (C/EBPβ) mRNAs are templates for the differential translation of several isoforms. Immunoblotting detects C/EBPαs with molecular masses of 42, 38, 30, and 20 kDa and C/EBPβs of 35, 20, and ~8.5 kDa. The DNA-binding activities and pool levels of p42(C/EBPα) and p30(C/EBPα) in control nuclear extracts decrease significantly whereas the binding activity and protein levels of the 20-kDa isoforms increase dramatically with LPS treatment. Our studies suggest that the LPS response involves alternative translational initiation at specific in-frame AUGs, producing specific C/EBPα and C/EBPβ isoform patterns. We propose that alternative translational initiation occurs by a leaky ribosomal scanning mechanism. We find that nuclear extracts from normal aged mouse livers have decreased p42(C/EBPα) levels and binding activity, whereas those of p20(C/EBPα) and p20(C/ESPβ) are increased. However, translation of 42-kDa C/EBPα is not down-regulated on polysomes, suggesting that aging may affect its nuclear translocation. Furthermore, recovery of the C/EBPα- and C/EBPβ- binding activities and pool levels from an LPS challenge is delayed significantly in aged mouse livers. Thus, aged livers have altered steady- state levels of C/EBPα and C/EBPβ isoforms. This result suggests that normal aging liver exhibits characteristics of chronic stress and a severe inability to recover from an inflammatory challenge.
AB - The CCAAT/enhancer binding protein α (C/EBPα) and CCAAT/enhancer binding protein β (C/EBPβ) mRNAs are templates for the differential translation of several isoforms. Immunoblotting detects C/EBPαs with molecular masses of 42, 38, 30, and 20 kDa and C/EBPβs of 35, 20, and ~8.5 kDa. The DNA-binding activities and pool levels of p42(C/EBPα) and p30(C/EBPα) in control nuclear extracts decrease significantly whereas the binding activity and protein levels of the 20-kDa isoforms increase dramatically with LPS treatment. Our studies suggest that the LPS response involves alternative translational initiation at specific in-frame AUGs, producing specific C/EBPα and C/EBPβ isoform patterns. We propose that alternative translational initiation occurs by a leaky ribosomal scanning mechanism. We find that nuclear extracts from normal aged mouse livers have decreased p42(C/EBPα) levels and binding activity, whereas those of p20(C/EBPα) and p20(C/ESPβ) are increased. However, translation of 42-kDa C/EBPα is not down-regulated on polysomes, suggesting that aging may affect its nuclear translocation. Furthermore, recovery of the C/EBPα- and C/EBPβ- binding activities and pool levels from an LPS challenge is delayed significantly in aged mouse livers. Thus, aged livers have altered steady- state levels of C/EBPα and C/EBPβ isoforms. This result suggests that normal aging liver exhibits characteristics of chronic stress and a severe inability to recover from an inflammatory challenge.
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M3 - Article
VL - 9
SP - 1479
EP - 1494
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 6
ER -