Rapamycin-sensitive induction of eukaryotic initiation factor 4F in regenerating mouse liver

Melissa M. Goggin, Christopher J. Nelsen, Scot Kimball, Leonard "Jim" Jefferson, Simon J. Morley, Jeffrey H. Albrecht

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Following acute injuries that diminish functional liver mass, the remaining hepatocytes substantially increase overall protein synthesis to meet increased metabolic demands and to allow for compensatory liver growth. Previous studies have not clearly defined the mechanisms that promote protein synthesis in the regenerating liver. In the current study, we examined the regulation of key proteins involved in translation initiation following 70% partial hepatectomy (PH) in mice. PH promoted the assembly of eukaryotic initiation factor (eIF) 4F complexes consisting of eIF4E, eIF4G, eIF4A1, and poly-A binding protein. eIF4F complex formation after PH occurred without detectable changes in eIF4E-binding protein 1 (4E-BP1) phosphorylation or its binding eIF4E. The amount of serine 1108-phosphorylated eIF4G (but not Ser209-phosphorylated eIF4E) was induced following PH. These effects were antagonized by treatment with rapamycin, indicating that target of rapamycin (TOR) activity is required for eIF4F assembly in the regenerating liver. Rapamycin inhibited the induction of cyclin D1, a known eIF4F-sensitive gene, at the level of protein expression but not messenger RNA (mRNA) expression. In conclusion, increased translation initiation mediated by the mRNA cap-binding complex eIF4F contributes to the induction of protein synthesis during compensatory liver growth. Further study of factors that regulate translation initiation may provide insight into mechanisms that govern metabolic homeostasis and regeneration in response to liver injury.

Original languageEnglish (US)
Pages (from-to)537-544
Number of pages8
JournalHepatology
Volume40
Issue number3
DOIs
StatePublished - Sep 1 2004

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Eukaryotic Initiation Factor-4F
Sirolimus
Hepatectomy
Liver
Proteins
RNA Caps
Poly(A)-Binding Proteins
Messenger RNA
Cyclin D1
Wounds and Injuries
Growth
Serine
Regeneration
Hepatocytes
Carrier Proteins
Homeostasis
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Goggin, Melissa M. ; Nelsen, Christopher J. ; Kimball, Scot ; Jefferson, Leonard "Jim" ; Morley, Simon J. ; Albrecht, Jeffrey H. / Rapamycin-sensitive induction of eukaryotic initiation factor 4F in regenerating mouse liver. In: Hepatology. 2004 ; Vol. 40, No. 3. pp. 537-544.
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Rapamycin-sensitive induction of eukaryotic initiation factor 4F in regenerating mouse liver. / Goggin, Melissa M.; Nelsen, Christopher J.; Kimball, Scot; Jefferson, Leonard "Jim"; Morley, Simon J.; Albrecht, Jeffrey H.

In: Hepatology, Vol. 40, No. 3, 01.09.2004, p. 537-544.

Research output: Contribution to journalArticle

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AU - Goggin, Melissa M.

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