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TGFβ signaling controls diverse normal developmental processes and pathogenesis of diseases including cancer and autoimmune and fibrotic diseases. TGFβ responses are generally mediated through transcriptional functions of Smads. A key step in TGFβ signaling is ligand-induced phosphorylation of receptor-activated Smads (R-Smads) catalyzed by the TGFβ type I receptor kinase. However, the potential of...
Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two α and two β subunits. Free α-hemoglobin (αHb) is unstable, and its precipitation contributes to the pathophysiology of β thalassemia. In erythrocytes, the α-hemoglobin stabilizing protein (AHSP) binds αHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-αHb reveals that AHSP specifically recognizes...
The ubiquitin-specific processing protease (UBP) family of deubiquitinating enzymes plays an essential role in numerous cellular processes. HAUSP, a representative UBP, specifically deubiquitinates and hence stabilizes the tumor suppressor protein p53. Here, we report the crystal structures of the 40 kDa catalytic core domain of HAUSP in isolation and in complex with ubiquitin aldehyde. These studies...
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