2009.10.02 – Cancer Research UK scientists identify a nuclear role for JAK2 in the phosphorylation of H3Y41

http://cancerology.blogspot.com/2009/10/new-data-for-jak2-kinase.html

Παρασκευή, 2 Οκτώβριος 2009

NEW DATA FOR JAK2 KINASE

2009.10.02 – Cancer Research UK scientists identify a nuclear role for JAK2 in the phosphorylation of H3Y41

01.10.09

Category: Scientific News

Results reveal a direct mechanistic link between two genes, JAK2 and LMO2, involved in normal hematopoiesis and leukemia

Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in hematological malignancies. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signaling cascades. In the 27 September 2009 edition of Nature advanced access publication, Dr Tony Kouzarides of the Gurdon Institute and Department of Pathology and colleagues from University of Cambridge, UK, show that human JAK2 is present in the nucleus of hematopoietic cells and directly phosphorylates Tyr-41 (Y41) on histone H3. Heterochromatin protein 1α (HP1α), but not HP1β, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukemic cells decreases both the expression of the hematopoietic oncogene LMO2 and the phosphorylation of H3Y41 at its promoter, simultaneously increasing the binding of HP1α at the same site. These results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, JAK2 and LMO2, involved in normal hematopoiesis and leukemia.

The scientists found that the enzyme made by the JAK2 gene is also located inside the cell nucleus and plays an important role in controlling how genetic information is used by the cell. Previously, it was only known to be located on the inner surface of cells – acting as a messenger between the outside of the cell and the cell’s nucleus. In this exciting research the authors have revealed new unidentified parts of the cell’s messaging system that can lead to leukemia, giving scientists new opportunities to develop drugs to block it.