Silencing of type II Phosphatidylinositol 4-kinase β stabilizes Prostate apoptosis response-4 and induces apoptosis in cancer cells.

Silencing of type II Phosphatidylinositol 4-kinase β stabilizes Prostate apoptosis response-4 and induces apoptosis in cancer cells. Biochem J. 2019 Jan 03;: Authors: Chaudhry S, Joshi V, Bojjireddy N, Thoh M, Sandur SK, Subrahmanyam G Abstract Type II Phosphatidylinositol 4-kinase β (PtdIns 4-kinase II β) is an enigma among the phosphatidylinositol 4-kinase family. The role of PtdIns 4-kinase II β in MCF-7 cells was addressed with the help of short hairpin RNA (shRNA). PtdIns 4-kinase II β shRNA transfection increased pan caspase activity and induced apoptosis in cancerous MCF-7 cells.  Non-cancerous MCF-10A cells were resistant to PtdIns 4-kinase II β shRNA induced apoptosis. Caspase 8 and 9 inhibitors rescued MCF-7 cells from apoptosis. Shotgun proteomic studies with Flag-tagged PtdIns 4-kinase II β immunoprecipitates showed tumor suppressor prostate apoptosis response-4 (Par-4) as one of the interacting proteins in HEK293 cells. In reciprocal experiments, Par-4 antibodies co-precipitated PtdIns 4-kinase II β from MCF-7 cells. Deletion of membrane localization motif (DCCPCC) or a mutation in ATP binding region (D304A) of PtdIns 4-kinase II β did not affect its interaction with Par-4. Pull down assays with GST-PtdIns 4-kinase II β truncated mutants showed the region between 101 to 215 amino acid residues is essential for interaction with Par-4. At molecular level, PtdIns 4-kinase II β shRNA transfection increased Par-4 ...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research