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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cbl proteins are ubiquitin protein ligases, which ubiquitinate activated tyrosine kinases and target them for degradation. Both c-Cbl and Cbl-b have an ubiquitin associated (UBA) domain at their C-terminal end. We observed that high molecular weight ubiquitinated proteins constitutively coimmunoprecipitated with transfected and endogenous Cbl-b, but not c-Cbl. The binding site for these ubiquitinated proteins was mapped to the UBA domain of Cbl-b (UBAb). GST-fusion proteins containing the UBAb interacted with ubiquitinated proteins and polyubiquitin chains in vitro, whereas those containing the UBA domain of c-Cbl (UBAc) did not. The UBAb had a much greater affinity for polyubiquitin chains than for monoubiquitin. Analysis of the UBAb and UBAc demonstrate that the affinity for ubiquitin is determined by multiple amino-acid differences between the two domains. Overexpression of the UBAb, but not overexpression of the UBAc, inhibited a variety of ubiquitin-mediated processes such as degradation of ubiquitinated proteins (i.e. EGFR, Mdm-2, and Siah-1). This in vivo result is consistent with the differences in ubiquitin binding observed in vitro between the UBAb and UBAc. This difference in ubiquitin-binding may reflect distinct regulatory functions of c-Cbl and Cbl-b.
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PMID:Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b. 1527 20

The innate immune system has been considered as an ancient system and less important than the adaptive immune system. However, the interest in innate immunity has grown significantly in the past few years marked by the identification of Toll-like receptors, a member of pattern recognition receptors (PRRs). The PRRs are crucial for the identification of self- and non-self-antigen and play a role in the initiation of signaling events that activate the effective immune response. These sensor signals through interweaving signaling cascades which result in the production of interferons and cytokines as the effector of immune system. Ubiquitin and ubiquitin-like modifiers (UBLs) actively mediate the rapid and versatile regulatory processes that initiate the activation of the innate immune system cascade. The seven in absentia homolog (SIAH) is a potent RING finger E3 ubiquitin ligase that is known to involve in several stress responses, including hypoxia, oxidative stress, DNA damage stress, and inflammation. In this review, the role of SIAH will be discussed as an E3 ubiquitin ligase on the regulation of innate immune.
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PMID:The role of E3 ubiquitin ligase seven in absentia homolog in the innate immune system: An overview. 3058 87