The peptidyl-prolyl isomerase Pin1 regulates granulocyte-macrophage colony-stimulating factor mRNA stability in T lymphocytes

Stephane Esnault, Zhong Jian Shen, Emily Whitesel, James S. Malter

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Abstract

Cytokine production is associated with both the normal and pathologic inflammatory response to injury. Previous studies have shown that the immunosuppressants cyclosporin A or FK506, which interact with the peptidyl-propyl isomerases cyclophilin A and FK506-binding protein (FKBP12), respectively, block cytokine expression. A third member of the peptidyl-propyl isomerase family, Pin1 is expressed by immune and other cells. Pin1 has been implicated in cell cycle progression, is overexpressed in human tumors, and may rescue neurons from τ-associated degeneration. However, the role of Pin1 in the immune system remains largely unknown. In this study, we analyze the role of Pin1 in GM-CSF expression by human PBMC and CD4+ lymphocytes. We show that Pin1 isomerase activity is necessary for activation-dependent, GM-CSF mRNA stabilization, accumulation, and protein secretion, but not non-AU-rich elements containing cytokine mRNAs, including TGF-β and IL-4. Mechanistically, Pin1 mediated the association of the AU-rich element-binding protein, AUF1, with GM-CSF mRNA, which determined the rate of decay by the exosome.

Original languageEnglish (US)
Pages (from-to)6999-7006
Number of pages8
JournalJournal of Immunology
Volume177
Issue number10
StatePublished - Nov 15 2006

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Peptidylprolyl Isomerase
Isomerases
RNA Stability
Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines
T-Lymphocytes
Messenger RNA
Tacrolimus Binding Protein 1A
AU Rich Elements
Cyclophilin A
Tacrolimus Binding Proteins
Exosomes
Nerve Degeneration
Tacrolimus
Immunosuppressive Agents
Interleukin-4
Cyclosporine
Immune System
Cell Cycle
Carrier Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

The peptidyl-prolyl isomerase Pin1 regulates granulocyte-macrophage colony-stimulating factor mRNA stability in T lymphocytes. / Esnault, Stephane; Shen, Zhong Jian; Whitesel, Emily; Malter, James S.

In: Journal of Immunology, Vol. 177, No. 10, 15.11.2006, p. 6999-7006.

Research output: Contribution to journalArticle

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