p300-mediated acetylation stabilizes the Th-inducing POK factor.

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Citation

Zhang M, Zhang J, Rui J, Liu X

p300-mediated acetylation stabilizes the Th-inducing POK factor.

J Immunol. 2010 Oct 1;185(7):3960-9. doi: 10.4049/jimmunol.1001462. Epub 2010 Sep 1.

PubMed ID
20810990 [ View in PubMed
]
Abstract

The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic differentiation of CD4 T cells. Although the regulation of ThPOK at the transcription level has been extensively studied, specific posttranslational modifications regulating the activity of ThPOK have not been addressed. In this paper, we show that ThPOK is an unstable protein that is more readily degraded in CD8 T cells compared with CD4 T cells. Among the various proteins that bind ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to arginines stabilizes ThPOK and enhances its ability to suppress the expression of CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an essential role of p300-mediated acetylation in regulating the stability of ThPOK and suggest that such regulation may play a part in CD4/CD8 lineage differentiation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Histone acetyltransferase p300Q09472Details