title: Molecular mechanisms of leukemia-associated protein degradation.
abstract: Chemical biology, using small molecules as probes to study the cellular signaling network, has developed rapidly in recent years. The interaction between chemistry and biology not only provides new insight into the understanding of cellular activities, but also generates new lead compounds for the treatment of diseases. Transcription factors and kinases such as retinoic acid receptor-alpha (RARα), acute myeloid leukemia 1 (AML1), CAAT/enhancer-binding protein α (C/EBPα), c-myc, and c-abl play important roles in the differentiation of hematopoietic stem/progenitor cells. Abnormalities in these proteins may cause the dysregulation of hematopoiesis and even the occurrence of leukemia. Ubiquitin-mediated protein degradation represents a critical mechanism in regulating the cellular levels and functions of these proteins. Thus, targeting protein degradation has been emerging as an important strategy to conquer malignant diseases. In this review, we will summarize the recent advances in the understanding of the roles of protein degradation in leukemia, with an emphasis on the mechanisms revealed by small molecules.
authors.affiliation: Department of Pathophysiology and Chemical Biology Division of Shanghai Universities E-Institutes, Key laboratory of Cell Differentiation and Apoptosis of the Ministry of Education of China, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Wu
authors.forename: Hu-Chen
authors.initials: HC
authors.lastname: Zhou
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
mesh_terms: D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
chemical_list: C107844:AML1-ETO fusion protein, human; D022763:CCAAT-Enhancer-Binding Protein-alpha; D050676:Core Binding Factor Alpha 2 Subunit; C489427:MYC protein, human; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; C000607071:RARA protein, human; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025801:Ubiquitin; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D011494:Protein Kinases; D016044:Fusion Proteins, bcr-abl