Editors' ChoiceIMMMUNOLOGY

Double-Duty Coactivator

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Science's STKE  30 May 2006:
Vol. 2006, Issue 337, pp. tw176
DOI: 10.1126/stke.3372006tw176

The protein OCA-B (Oct coactivator from B cells; also known as OBF-1, for OCT-binding factor-1, and Bob1) is a transcriptional coactivator. Thus, when Siegel et al. explored B cell development in cells from Oca-b–/– mice, they were surprised to find that the primary effect of OCA-B on abundance of the tyrosine kinase Syk [which mediates signaling from the B cell receptor (BCR) and pre-BCR (a variant of the BCR formed during the pre-B cell stage of B cell development)] was regulated not by a transcriptional mechanism but rather through a direct interaction of OCA-B with Syk. Analysis of the Oca-b–/– animals showed that OCA-B functions in the development of pre-B cells. The Oca-b–/– pre-B cells showed increased proliferation when exposed to interleukin 7 and other properties consistent with defective signaling by the pre-BCR. This appeared to be partly caused by loss of Syk. Although the abundance of Syk mRNA was reduced, the authors suspected a nontranscriptional mode of regulation because OCA-B appeared not to occupy predicted binding sites in the Syk promoter. The stability of Syk protein is regulated through proteasome-dependent degradation, and immunoblotting showed that the stability of Syk was decreased in B cells stimulated through the BCR and exposed to cycloheximide to inhibit protein synthesis. Syk was immunoprecipitated with OCA-B from splenocytes, and in vitro binding assays with GST (glutathione S-transferase)-tagged Syk and OCA-B expressed in bacteria showed that the two proteins interacted. Interaction of the endogenous proteins was also indicated by immunoprecipitation studies in a human Burkitt's lymphoma B cell line. Thus, the authors propose that OCA-B works on two fronts to regulate B cell development and BCR signaling. In its originally described role, it regulates expression of genes involved in cell signaling. The new data show that it may also promote BCR signaling by interacting in the cytoplasm with Syk and stabilizing the kinase so that it is ready to transmit signals from the BCR.

R. Siegel, U. Kim, A. Patke, X. Yu, X. Ren, A. Tarakhovsky, R. G. Roeder, Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development. Cell 125, 761-774 (2006). [PubMed]

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