![]() Increasing evidence accumulates that ubiquitin-ligases termed mammalian seven in absentia homologs (SIAHs) are not only critical for the pathogenesis of solid tumors but also for leukemogenesis. Therefore, pharmacological modulation of these proteins could allow a specific level of control. Ubiquitin-ligases selectively bind substrates to target them for poly-ubiquitinylation and proteasomal degradation. As dysregulation of the UPS is observed in most cancers including leukemia, the UPS is a valid target for therapeutic intervention strategies. The ubiquitin–proteasome system (UPS) is a major pathway for the proteolytic degradation of cellular proteins. Proteases act in an irreversible manner and therefore have to be strictly regulated. The delicate balance between the synthesis and the degradation of proteins ensures cellular homeostasis.
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