CUL1 explained

Cullin 1, also known as CUL1, is a human protein and gene from cullin family.This protein plays an important role in protein degradation and protein ubiquitination.

This is an essential component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, it serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme.

This protein is a part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2. It also interacts with RNF7. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction negatively regulates the association with SKP1 in the SCF complex. Interacts with COPS2. It is expressed in lung fibroblasts.

The protein is neddylated, which enhances the ubiquitination activity of SCF. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.

Further reading

• Kipreos ET, Lander LE, Wing JP . cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. . Cell . 85 . 6 . 829–39 . 1996 . 8681378 . 10.1016/S0092-8674(00)81267-2 . 15805562 . etal. free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Lisztwan J, Marti A, Sutterlüty H . Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway. . EMBO J. . 17 . 2 . 368–83 . 1998 . 9430629 . 10.1093/emboj/17.2.368 . 1170388 . etal.
• Michel JJ, Xiong Y . Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A. . Cell Growth Differ. . 9 . 6 . 435–49 . 1998 . 9663463 .
• Ng RW, Arooz T, Yam CH . Characterization of the cullin and F-box protein partner Skp1. . FEBS Lett. . 438 . 3 . 183–9 . 1998 . 9827542 . 10.1016/S0014-5793(98)01299-X . 40950881 . etal. free .
• Winston JT, Strack P, Beer-Romero P . The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. . Genes Dev. . 13 . 3 . 270–83 . 1999 . 9990852 . 10.1101/gad.13.3.270 . 316433 . etal.
• Tan P, Fuchs SY, Chen A . Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. . Mol. Cell . 3 . 4 . 527–33 . 1999 . 10230406 . 10.1016/S1097-2765(00)80481-5 . etal. free .
• Ohta T, Michel JJ, Schottelius AJ, Xiong Y . ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. . Mol. Cell . 3 . 4 . 535–41 . 1999 . 10230407 . 10.1016/S1097-2765(00)80482-7 . 19371828 . free .
• Marti A, Wirbelauer C, Scheffner M, Krek W . Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation. . Nat. Cell Biol. . 1 . 1 . 14–9 . 1999 . 10559858 . 10.1038/8984 . 8884226 .
• Hori T, Osaka F, Chiba T . Covalent modification of all members of human cullin family proteins by NEDD8. . Oncogene . 18 . 48 . 6829–34 . 2000 . 10597293 . 10.1038/sj.onc.1203093 . 22861534 . etal.
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• Morimoto M, Nishida T, Honda R, Yasuda H . Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the activity of SCF(skp2) toward p27(kip1). . Biochem. Biophys. Res. Commun. . 270 . 3 . 1093–6 . 2000 . 10772955 . 10.1006/bbrc.2000.2576 .
• Swaroop M, Wang Y, Miller P . Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation. . Oncogene . 19 . 24 . 2855–66 . 2000 . 10851089 . 10.1038/sj.onc.1203635 . 2100588 . etal.
• Furukawa M, Zhang Y, McCarville J . The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1. . Mol. Cell. Biol. . 20 . 21 . 8185–97 . 2000 . 11027288 . 10.1128/MCB.20.21.8185-8197.2000 . 86428 . etal.
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination. . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Wiemann S, Weil B, Wellenreuther R . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 . etal.
• Lyapina S, Cope G, Shevchenko A . Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. . Science . 292 . 5520 . 1382–5 . 2001 . 11337588 . 10.1126/science.1059780 . 2001Sci...292.1382L . 14224920 . etal.
• Fukuchi M, Imamura T, Chiba T . Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins. . Mol. Biol. Cell . 12 . 5 . 1431–43 . 2001 . 11359933 . 10.1091/mbc.12.5.1431. 34595 . etal.
• Senadheera D, Haataja L, Groffen J, Heisterkamp N . The small GTPase Rac interacts with ubiquitination complex proteins Cullin-1 and CDC23. . Int. J. Mol. Med. . 8 . 2 . 127–33 . 2001 . 11445862 . 10.3892/ijmm.8.2.127.
• Kiernan RE, Emiliani S, Nakayama K . Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome. . Mol. Cell. Biol. . 21 . 23 . 7956–70 . 2001 . 11689688 . 10.1128/MCB.21.23.7956-7970.2001 . 99964 . etal.