Lymphocyte Signaling

PU.1 is a member of the Ets family of transcription factors and activates target genes through the purine-rich PU-box (1). PU.1 plays a pivotal role in the differentiation of myeloid cells and lymphocytes and is expressed in several hematopoietic cells including B lymphocytes, macrophages, neutrophils, mast cells, early erythroid cells and megakaryocytes (1,2). The concentration of PU.1 is critical for both the determination of hematopoietic cell lineage and the regulation of differentiation versus stem cell proliferation (3,4). In addition, PU.1 activity is influenced by phosphorylation and interactions with other hematopoietic transcription factors. Phosphorylation of PU.1 at Ser146 by CK2 promotes binding to IRF4 and synergistic activation through the immunoglobulin κ 3' enhancer (5). Treatment of pro-B cells with IL-3 leads to phosphorylation of PU.1 at Ser140, resulting in increased PU.1 activity and activation of the anti-apoptotic gene MCL-1 (6). GATA1 binding blocks PU.1 activity during erythroid cell development (7). Overexpression of PU.1 resulting from proviral insertion during Friend virus infection can induce erythroleukemia, while reduced expression has been associated with acute myeloid leukemia (8).

1. Lloberas, J. et al. (1999) Immunol. Today 20, 184-189.
2. Klemsz, M.J. et al. (1990) Cell 61, 113-124.
3. Dahl, R. and Simon, M.C. (2003) Blood Cells Mol. Dis. 31, 229-233.
4. DeKoter, R.P. and Singh, H. (2000) Science 288, 1439-1441.
5. Pongubala, J.M. et al. (1993) Science 259, 1622-1625.
6. Wang, J.M. et al. (2003) Mol. Cell Biol. 23, 1896-1909.
7. Zhang, P. et al. (1999) Proc. Natl. Acad. Sci. USA 96, 8705-8710.
8. Moreau-Gachelin, F. et al. (1998) Nature 331, 277-280.

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PU.1 Blocking Peptide

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