By P. P. Pandolfi (auth.), Pier Paolo Pandolfi MD, Ph.D., Peter K. Vogt Ph.D. (eds.)
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Additional resources for Acute Promyelocytic Leukemia: Molecular Genetics, Mouse Models and Targeted Therapy
The transcription factor GATA2, which is important for hematopoietic progenitor cell commitment , also interacts with PLZF, leading to a block in GATA2-mediated transactivation . The effect of these interactions on PLZF repression activity has not been described, but downregulation of the action of other factors is a signiﬁcant way in which PLZF could modulate hematopoietic development. Interestingly, both a physical interaction and functional crosstalk between RARα and GATA2 has been described in myeloid differentiation , suggesting that regulation of this process by PLZF would have a signiﬁcant role in normal and malignant hematopoiesis.
Unresolved questions in regard to PLZF include its exact mode of repression, and key transcriptional targets and physiological stimuli that lead to its posttranslational modiﬁcation and subsequent regulation of transcriptional function. References 1. 2. 3. 4. 5. 6. Ball HJ, Melnick A, Shaknovich R, Kohanski RA, Licht JD (1999) The promyelocytic leukemia zinc ﬁnger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase. Nucleic Acids Res 27:4106–4113 Reference deleted in proof Barna M, Hawe N, Niswander L, Pandolﬁ PP (2000) Plzf regulates limb and axial skeletal patterning.
J. McConnell · J. D. Licht There is a growing body of evidence that, in addition to the nucleus, PLZF can be found in the cytoplasm. In a process called “ectodomain shedding,” a membrane-anchored ligand for the epidermal growth factor receptor (EGFR) HB-EGF (heparin-binding EGF-like growth factor) is cleaved, generating a small, roughly 7-kDa fragment of HB-EGF in the cytoplasm of the cell. This translocates to the nucleus where it binds PLZF through the ﬁrst three (N-terminal) zinc ﬁngers of PLZF [60, 61].