Role of E6AP in Malignancies and Tumorigenesis

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Leukemia is a malignant hematological disorder characterized by proliferation of abnormal white cells that infiltrate the bone marrow, peripheral blood and other important organs. Leukemia arising from myeloid cells is known as Myeloid Leukemia which may either be chronic myeloid leukemia (CML) and/or acute myeloid leukemia (AML). AML is a complex disease caused by mutations, deregulated gene expression and epigenetic modifications leading to increased proliferation and decreased differentiation of hematopoietic progenitor cells. Several important molecular markers have been discovered in AML to better characterize patients. C/EBPα is an important regulator of Granulopoiesis.

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The RING domain provides a docking site for the E2 enzyme, which mediate transfer of ubiquitin to the substrate, facilitating assembly of mono- or polyubiquitylated conjugates via different lysine residues of ubiquitin. The resulting modifications have a diverse range of biological functions, from proteasome-dependent proteolysis (Lys48- and Lys 11-linked polyubiquitin) to post-translational regulation of protein function, structure, assembly, and/or localization (Lys 63 and other linkages)[1, 6]. E3 ligases can also be classified into single subunit E3s (e.g. Mdm2, Cbl) and multi-subunit complexes (APC, SCF). E3 enzymes bind their target substrates through various protein-protein interaction domains (e.g.

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Due to the above relevance and role of E6AP in malignancies and tumorigenesis .. . 1) Expression of GST and GST-E6AP plasmids in BL21 strain of . 2) Purification of GST and GST-E6AP proteins from BL21 strain of . 3) Validation of expression through western blotting . 4) To detect GST-E6AP protein interaction with whole cell lysates of HL-60 cells treated with 1μM ATRA for 0, 24 and 48 hrs .

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