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Molecular mechanisms of leukemia-associated protein
degradation |
| Ying-Li WU1,Guo-Qiang CHEN1,Hu-Chen ZHOU2, |
| 1.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; 2.The School of Pharmacy
and E-Institute of Chemical Biology, Shanghai JiaoTong University,
Shanghai 200240, China; |
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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.
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| Keywords
protein degradation
leukemia
chemical biology
transcription factors
oncoprotein
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Issue Date: 05 December 2010
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