Protein IsG15 Modification in the Development and the Treatment of Chronic Myeloid Leukemia

摘要

Interferons are useful drugs in treating chronic myeloid leukemia (CML). One of the cellular responses of interferon treatment is the activation of protein modification by ISO 15. We have cloned a novel gene encoding a protease UBP43 that specifically removes 15015 from 15015 modified proteins. Furthermore, we have generated UBP43 knockout mice. UBP43 deficient hematopoietic cells have much higher levels of ISO 15 modified proteins upon interferon stimulation and are hypersensitive to interferon treatment. This grant is to demonstrate that protein ISG15 modification is crucial for interferon function in CML treatment and to analyze the effect of UBP43 on CML development. In the past funding period, we have established BCR/ABL positive leukemia cell lines that have higher than normal or lower than normal level of ISG15 conjugation and initiated the characterization of these cell lines. Furthermore, we have generated additional important data to support that UBP43 knockout mice are resistant to BCR/ABL induced CML development and that interferon plays a critical role in this process. We will continue to perform experiments as proposed in the application to establish the role of 15015 modification and UBP43 in interferon signaling and CML development.