Ecdysteroid chemistry and biochemistry

The 19S regulatory particle is responsible for stimulating the 20S to degrade proteins. A primary function of the 19S regulatory ATPases is to open the gate in the 20S that blocks the entry of substrates into the degradation chamber. [33] The mechanism by which the proteasomal ATPase open this gate has been recently elucidated. [16] 20S gate opening, and thus substrate degradation, requires the C-termini of the proteasomal ATPases, which contains a specific motif (., HbYX motif). The ATPases C-termini bind into pockets in the top of the 20S, and tether the ATPase complex to the 20S proteolytic complex, thus joining the substrate unfolding equipment with the 20S degradation machinery. Binding of these C-termini into these 20S pockets by themselves stimulates opening of the gate in the 20S in much the same way that a "key-in-a-lock" opens a door. [16] The precise mechanism by which this "key-in-a-lock" mechanism functions has been structurally elucidated. [34]

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More recently, an interaction between USP7 and the EBNA1 protein of Epstein-Barr virus (EBV) (another herpesvirus ) was also discovered. [13] This interaction is particularly interesting given the oncogenic potential (potential to cause cancer) of EBV, which is associated with several human cancers. EBNA1 can compete with p53 for binding USP7. Stabilization by USP7 is important for the tumor suppressor function of p53. In cells, EBNA1 can sequester USP7 from p53 and thus attenuate stabilization of p53, rendering the cells predisposed to turning cancerous. Compromising the function of p53 by sequestering USP7 is one way EBNA1 can contribute to the oncogenic potential of EBV. Additionally, human USP7 was also shown to form a complex with GMPS and this complex is recruited to EBV genome sequences. [14] USP7 was shown to be important for histone H2B deubiquitination in human cells and for deubiquitination of histone H2B incorporated in the EBV genome. Thus USP7 may also be important for regulation of viral gene expression.

Ecdysteroid chemistry and biochemistry

ecdysteroid chemistry and biochemistry

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