cullin protein
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2015 ◽  
Vol 27 (3) ◽  
pp. 741-753 ◽  
Author(s):  
Julia Mergner ◽  
Stephanie Heinzlmeir ◽  
Bernhard Kuster ◽  
Claus Schwechheimer

2011 ◽  
Vol 22 (24) ◽  
pp. 4706-4715 ◽  
Author(s):  
Yin Yin Choo ◽  
Boon Kim Boh ◽  
Jessica Jie Wei Lou ◽  
Jolane Eng ◽  
Yee Chin Leck ◽  
...  

Cullin RING ligases (CRLs) are the largest family of cellular E3 ubiquitin ligases and mediate polyubiquitination of a number of cellular substrates. CRLs are activated via the covalent modification of the cullin protein with the ubiquitin-like protein Nedd8. This results in a conformational change in the cullin carboxy terminus that facilitates the ubiquitin transfer onto the substrate. COP9 signalosome (CSN)-mediated cullin deneddylation is essential for CRL activity in vivo. However, the mechanism through which CSN promotes CRL activity in vivo is currently unclear. In this paper, we provide evidence that cullin deneddylation is not intrinsically coupled to substrate polyubiquitination as part of the CRL activation cycle. Furthermore, inhibiting substrate-receptor autoubiquitination is unlikely to account for the major mechanism through which CSN regulates CRL activity. CSN also did not affect recruitment of the substrate-receptor SPOP to Cul3, suggesting it may not function to facilitate the exchange of Cul3 substrate receptors. Our results indicate that CSN binds preferentially to CRLs in the neddylation-induced, active conformation. Binding of the CSN complex to active CRLs may recruit CSN-associated proteins important for CRL regulation. The deneddylating activity of CSN would subsequently promote its own dissociation to allow progression through the CRL activation cycle.


2011 ◽  
Vol 12 (4) ◽  
pp. 220 ◽  
Author(s):  
Antonio Sarikas ◽  
Thomas Hartmann ◽  
Zhen-Qiang Pan

2001 ◽  
Vol 12 (12) ◽  
pp. 3839-3851 ◽  
Author(s):  
Zhanyun Tang ◽  
Bing Li ◽  
Rajnish Bharadwaj ◽  
Haizhen Zhu ◽  
Engin Özkan ◽  
...  

In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. With the use of a baculoviral expression system, we have reconstituted the ubiquitin ligase activity of human APC. In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. However, the minimal APC2/11 ubiquitin ligase module does not possess substrate specificity, because it also ubiquitinates the destruction box deletion mutants of securin and cyclin B1. Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. Zn2+-binding and mutagenesis experiments indicate that APC11 binds Zn2+at a 1:3 M ratio. Unlike the two Zn2+ ions of the canonical RING-finger motif, the third Zn2+ ion of APC11 is not essential for its ligase activity. Surprisingly, with Ubc4 as the E2 enzyme, Zn2+ ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn2+ ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis.


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