Thr 163 Phosphorylation Causes Mcl-1 Stabilization when Degradation Is Independent of the Adjacent GSK3-Targeted Phosphodegron, Promoting Drug Resistance in Cancer

• Published in: PloS one Vol. 7; no. 10; p. e47060
• Main Authors: Nifoussi, Shanna K., Vrana, Julie A., Domina, Aaron M., De Biasio, Alfredo, Gui, Jingang, Gregory, Mark A., Hann, Stephen R., Craig, Ruth W.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.10.2012; Public Library of Science (PLoS)
• Subjects: Acetic acid; Activation; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Bcl-2 protein; Biology; Blotting, Western; Burkitt's lymphoma; Cancer; Cell cycle; Cell death; Cell Line, Tumor; Chemotherapy; CHO Cells; Cisplatin; Cisplatin - pharmacology; Cotton, Norris; Cricetinae; Cytarabine - pharmacology; Degradation; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug therapy; Etoposide; Etoposide - pharmacology; Extracellular signal-regulated kinase; Fibroblasts; Flow Cytometry; Glutamic acid; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen synthesis; Humans; Kinases; Laboratories; Leukemia; Lymphoma; Lymphomas; Mcl-1 protein; Medicine; MicroRNAs; Mutation; Myeloid Cell Leukemia Sequence 1 Protein; Organic acids; Pests; Phosphorylation; Proline; Protein Stability; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Sequences; Serine; Signal transduction; Stabilization; Threonine; Threonine - metabolism; Toxicology; Vinblastine; Vinblastine - pharmacology; Lebanon; United States > US; New Hampshire
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047060

The antiapoptotic Bcl-2 family member Mcl-1 is a PEST protein (containing sequences enriched in proline, glutamic acid, serine, and threonine) and is subject to rapid degradation via multiple pathways. Impaired degradation leading to the maintenance of Mcl-1 expression is an important determinant of...