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Traf1 Induction and Protection from Tumor Necrosis Factor by Nuclear Factor-B p65 Is Independent of Serine 536 Phosphorylation

Laboratory of Immunology, National Institute on Aging, Baltimore, Maryland

Requests for reprints: Carl Y. Sasaki, Laboratory of Immunology, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224. Phone: 410-558-8096; Fax: 410-558-8284; E-mail: sasakic{at}grc.nia.nih.gov.

Abnormal nuclear factor-B (NF-B) signaling has been attributed to the initiation and progression of cancer. Posttranslational modification of p65 facilitates optimal NF-B signaling after activation. Here, we show that the phosphorylation of serine 536 was required for p65-mediated transcription and IB expression in fibroblasts. Furthermore, tumor necrosis factor (TNF) treatment slightly induced p65 phosphorylation, and both unphosphorylated and phosphorylated p65 translocated into the nucleus. The phosphorylation of serine 536 was not required for p65-mediated protection from TNF cytotoxicity and Traf1 induction in fibroblasts. Also, the corecruitment of p65 and RNA polymerase II to the Traf1 enhancer region did not require p65 phosphorylation. However, the corecruitment of p65 and RNA polymerase II to the Csf2 promoter required the phosphorylation of serine 536. These findings suggested that the requirement of serine phosphorylation at residue 536 and the distance between the NF-B response element and the start of transcription may influence which genes will be transcribed. [Cancer Res 2007;67(23):11218–25]