Biology:Cullin
| Cullin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex | |||||||||
| Identifiers | |||||||||
| Symbol | Cullin | ||||||||
| Pfam | PF00888 | ||||||||
| InterPro | IPR001373 | ||||||||
| PROSITE | PDOC00967 | ||||||||
| SCOP2 | 1ldj / SCOPe / SUPFAM | ||||||||
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| Cullin protein neddylation domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex | |||||||||
| Identifiers | |||||||||
| Symbol | Cullin_Nedd8 | ||||||||
| Pfam | PF10557 | ||||||||
| InterPro | IPR019559 | ||||||||
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Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination.[1][2]
The human genome contains eight cullin genes
- CUL1, part of SCF complex
- CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box)
- CUL3, part of CUL3-BTB complex
- CUL4A
- CUL4B
- CUL5
- CUL7
- CUL9, also known as PARC
There is also a more distant member called ANAPC2 (or APC2), part of the Anaphase-promoting complex.
CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex.
Cullin-RING ubiquitin ligases
Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms.[3] The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as CUL9, also known as p53 cytoplasmic anchor PARC, and the ANAPC2 subunit of the anaphase-promoting complex/cyclosome; both CUL9 and ANAPC2 have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins.[4][5][6]
Modification by NEDD8
With the exception of ANAPC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Nedd8/Rub1 is a small ubiquitin-like protein, which was originally found to be conjugated to Cdc53, a cullin component of the SCF (Skp1-Cdc53/CUL1-F-box protein) E3 Ub ligase complex in Saccharomyces cerevisiae (Baker's yeast), and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue.[7]
References
- ↑ Bosu, Dimple R.; Kipreos, Edward T. (2008). "Cullin-RING ubiquitin ligases: Global regulation and activation cycles". Cell Division 3: 7. doi:10.1186/1747-1028-3-7. PMID 18282298.
- ↑ Bruce, Alberts (2014-11-18). Molecular biology of the cell (Sixth ed.). New York, NY. ISBN 9780815344322. OCLC 887605755.
- ↑ "cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family". Cell 85 (6): 829–39. June 1996. doi:10.1016/S0092-8674(00)81267-2. PMID 8681378.
- ↑ "Function and regulation of cullin-RING ubiquitin ligases". Nat. Rev. Mol. Cell Biol. 6 (1): 9–20. January 2005. doi:10.1038/nrm1547. PMID 15688063. https://authors.library.caltech.edu/55905/2/nrm1547-S1.pdf.
- ↑ "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex". Nature 416 (6882): 703–9. April 2002. doi:10.1038/416703a. PMID 11961546. Bibcode: 2002Natur.416..703Z.
- ↑ "Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases". Cell 119 (4): 517–28. November 2004. doi:10.1016/j.cell.2004.10.019. PMID 15537541.
- ↑ "Nedd8 on cullin: building an expressway to protein destruction". Oncogene 23 (11): 1985–97. March 2004. doi:10.1038/sj.onc.1207414. PMID 15021886.
External links
- Cullin family - Sanger Institute website.
- Cullin+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
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