Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130) [Investigation Report]

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Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130) [Investigation Report]

On September 8, 2013, Posted by , In BIO, By ,,,,,,,, , With Comments Off on Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130) [Investigation Report]

  1. Thilo Hagen*

  1. Section of Biochemistry, Yong Loo Lin College of Medication, Countrywide University of Singapore, Singapore 117597, Singapore
  1. *Creator for correspondence (thilo_hagenatnuhs.edu.sg)

Cullin-RING ubiquitin ligases (CRLs) mediate the ubiquitination of many protein substrates and focus on them for proteasomal
degradation. The function of CRLs is underneath tight regulation by Cullin-binding proteins. It has been noted that the Spliceosome-connected
protein one hundred thirty (SAP130/SF3b-3) binds to several Cullin proteins, but it remains mysterious regardless of whether SAP130 performs any part in regulating
the purpose of CRLs. Right here, we report that SAP130 overexpression decreases the binding of adaptor protein Skp1 and substrate
receptor Skp2 to Cul1, while it has no impact on CAND1 binding to Cul1. Overexpression of SAP130 decreases the degradation
rate of p27, a protein substrate of the SCFSkp2 ligase. Interestingly, silencing of SAP130 also inhibits the degradation of p27, suggesting a twin part for SAP130 in the
regulation of SCF action. We hypothesized that the regulatory function of SAP130 could increase to other CRLs nonetheless, overexpression
of SAP130 is unable to have an effect on the protein security of the Cul2 and Cul3 substrates, HIF-one and NRF-two. SAP130 binds to Cul1,
Cul2 and Cul4 with comparable affinity, and it binds to Cul3 a lot more strongly. SAP130 localizes in both the nucleus and the cytoplasm.
Consequently, the incapacity of SAP130 to regulate Cul2 and Cul3 CRLs cannot be described by reduced binding affinity of SAP130 to these
cullins or by subcellular sequestration of SAP130. We suggest a novel position for SAP130 in the regulation of SCF, whereby SAP130
physically competes with the adaptor protein/F-box protein for Cul1 binding and interferes with the assembly of a useful
SCF ligase.

  • Received February nine, 2013.
  • Acknowledged June four, 2013.

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