CDC34 explained

CDC34 is a gene that in humans encodes the protein Ubiquitin-conjugating enzyme E2 R1.^{[1] [2] [3]} This protein is a member of the ubiquitin-conjugating enzyme family, which catalyzes the covalent attachment of ubiquitin to other proteins.^[4]

CDC34 was originally discovered by work in baker's yeast as a gene that is essential for the cell cycle.^[5] Cdc34 in yeast targets numerous substrates - notably the cyclin-dependent kinase inhibitor Sic1^[6] - for ubiquitin-mediated protein degradation.^[7] CDC34 is required for ubiquitin-mediated degradation of cell cycle G1 regulators, and for the initiation of DNA replication.^[8]

Interactions

CDC34 has been shown to interact with CSNK2B,^[9] BTRC^{[10] [11]} and CDK9.^[12]

Further reading

• King RW, Deshaies RJ, Peters JM, Kirschner MW . How proteolysis drives the cell cycle . Science . 274 . 5293 . 1652–9 . December 1996 . 8939846 . 10.1126/science.274.5293.1652 . 25369228 . 1996Sci...274.1652K .
• Pagano M . Cell cycle regulation by the ubiquitin pathway . FASEB Journal . 11 . 13 . 1067–75 . November 1997 . 9367342 . 10.1096/fasebj.11.13.9367342 . free . 6368478 .
• Lisztwan J, Marti A, Sutterlüty H, Gstaiger M, Wirbelauer C, Krek W . 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 . The EMBO Journal . 17 . 2 . 368–83 . January 1998 . 9430629 . 1170388 . 10.1093/emboj/17.2.368 .
• Song A, Wang Q, Goebl MG, Harrington MA . Phosphorylation of nuclear MyoD is required for its rapid degradation . Molecular and Cellular Biology . 18 . 9 . 4994–9 . September 1998 . 9710583 . 109084 . 10.1128/mcb.18.9.4994 .
• Gonen H, Bercovich B, Orian A, Carrano A, Takizawa C, Yamanaka K, Pagano M, Iwai K, Ciechanover A . Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha . The Journal of Biological Chemistry . 274 . 21 . 14823–30 . May 1999 . 10329681 . 10.1074/jbc.274.21.14823 . free .
• Pati D, Meistrich ML, Plon SE . Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis . Molecular and Cellular Biology . 19 . 7 . 5001–13 . July 1999 . 10373550 . 84326 . 10.1128/mcb.19.7.5001 .
• Seol JH, Feldman RM, Zachariae W, Shevchenko A, Correll CC, Lyapina S, Chi Y, Galova M, Claypool J, Sandmeyer S, Nasmyth K, Deshaies RJ, Shevchenko A, Deshaies RJ . Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34 . Genes & Development . 13 . 12 . 1614–26 . June 1999 . 10385629 . 316801 . 10.1101/gad.13.12.1614 .
• Read MA, Brownell JE, Gladysheva TB, Hottelet M, Parent LA, Coggins MB, Pierce JW, Podust VN, Luo RS, Chau V, Palombella VJ . Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha . Molecular and Cellular Biology . 20 . 7 . 2326–33 . April 2000 . 10713156 . 85397 . 10.1128/MCB.20.7.2326-2333.2000 .
• Reymond F, Wirbelauer C, Krek W . Association of human ubiquitin-conjugating enzyme CDC34 with the mitotic spindle in anaphase . Journal of Cell Science . 113 (Pt 10) . 10 . 1687–94 . May 2000 . 10.1242/jcs.113.10.1687 . 10769200 . free .
• Charrasse S, Carena I, Brondani V, Klempnauer KH, Ferrari S . Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement of the Cdc34-SCF(p45Skp2) pathway . Oncogene . 19 . 26 . 2986–95 . June 2000 . 10871850 . 10.1038/sj.onc.1203618 . free .
• Strack P, Caligiuri M, Pelletier M, Boisclair M, Theodoras A, Beer-Romero P, Glass S, Parsons T, Copeland RA, Auger KR, Benfield P, Brizuela L, Rolfe M . SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4 . Oncogene . 19 . 31 . 3529–36 . July 2000 . 10918611 . 10.1038/sj.onc.1203647 . free .
• Duan W, Sun B, Li TW, Tan BJ, Lee MK, Teo TS . Cloning and characterization of AWP1, a novel protein that associates with serine/threonine kinase PRK1 in vivo . Gene . 256 . 1–2 . 113–21 . October 2000 . 11054541 . 10.1016/S0378-1119(00)00365-6 .
• Block K, Boyer TG, Yew PR . Phosphorylation of the human ubiquitin-conjugating enzyme, CDC34, by casein kinase 2 . The Journal of Biological Chemistry . 276 . 44 . 41049–58 . November 2001 . 11546811 . 10.1074/jbc.M106453200 . free .
• Wu K, Chen A, Tan P, Pan ZQ . The Nedd8-conjugated ROC1-CUL1 core ubiquitin ligase utilizes Nedd8 charged surface residues for efficient polyubiquitin chain assembly catalyzed by Cdc34 . The Journal of Biological Chemistry . 277 . 1 . 516–27 . January 2002 . 11675391 . 10.1074/jbc.M108008200 . free .
• Kiernan RE, Emiliani S, Nakayama K, Castro A, Labbé JC, Lorca T, Nakayama Ki K, Benkirane M . Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome . Molecular and Cellular Biology . 21 . 23 . 7956–70 . December 2001 . 11689688 . 99964 . 10.1128/MCB.21.23.7956-7970.2001 .
• Semplici F, Meggio F, Pinna LA, Oliviero S . CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TrCP and enhances beta-catenin degradation . Oncogene . 21 . 25 . 3978–87 . June 2002 . 12037680 . 10.1038/sj.onc.1205574 . free .

Notes and References

1. Plon SE, Leppig KA, Do HN, Groudine M . Cloning of the human homolog of the CDC34 cell cycle gene by complementation in yeast . Proceedings of the National Academy of Sciences of the United States of America . 90 . 22 . 10484–8 . November 1993 . 8248134 . 47801 . 10.1073/pnas.90.22.10484 . 1993PNAS...9010484P . free .
2. Gazdoiu S, Yamoah K, Wu K, Escalante CR, Tappin I, Bermudez V, Aggarwal AK, Hurwitz J, Pan ZQ . Proximity-induced activation of human Cdc34 through heterologous dimerization . Proceedings of the National Academy of Sciences of the United States of America . 102 . 42 . 15053–8 . October 2005 . 16210246 . 1242854 . 10.1073/pnas.0507646102 . 2005PNAS..10215053G . free .
3. Web site: Entrez Gene: CDC34 cell division cycle 34 homolog (S. cerevisiae).
4. Goebl MG, Yochem J, Jentsch S, McGrath JP, Varshavsky A, Byers B . The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme . Science . 241 . 4871 . 1331–5 . September 1988 . 2842867 . 10.1126/science.2842867 . 1988Sci...241.1331G .
5. Dutcher SK, Hartwell LH . The role of S. cerevisiae cell division cycle genes in nuclear fusion . Genetics . 100 . 2 . 175–84 . February 1982 . 10.1093/genetics/100.2.175 . 7049831 . 1201806 .
6. King RW, Deshaies RJ, Peters JM, Kirschner MW . How proteolysis drives the cell cycle . Science . 274 . 5293 . 1652–9 . December 1996 . 8939846 . 10.1126/science.274.5293.1652 . 1996Sci...274.1652K . 25369228 .
7. Williams KM, Qie S, Atkison JH, Salazar-Arango S, Alan Diehl J, Olsen SK . Structural insights into E1 recognition and the ubiquitin-conjugating activity of the E2 enzyme Cdc34 . Nature Communications . 10 . 1 . 3296 . July 2019 . 31341161 . 10.1038/s41467-019-11061-8 . 6656757 . 2019NatCo..10.3296W . free .
8. Web site: Entrez Gene: CDC34 cell division cycle 34 homolog (S. cerevisiae).
9. Block K, Boyer TG, Yew PR . Phosphorylation of the human ubiquitin-conjugating enzyme, CDC34, by casein kinase 2 . The Journal of Biological Chemistry . 276 . 44 . 41049–58 . November 2001 . 11546811 . 10.1074/jbc.M106453200 . free .
10. Semplici F, Meggio F, Pinna LA, Oliviero S . CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TrCP and enhances beta-catenin degradation . Oncogene . 21 . 25 . 3978–87 . June 2002 . 12037680 . 10.1038/sj.onc.1205574 . free .
11. Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M . Identification of a family of human F-box proteins . Current Biology . 9 . 20 . 1177–9 . October 1999 . 10531035 . 10.1016/S0960-9822(00)80020-2 . 7467493 . free . 1999CBio....9.1177C .
12. Kiernan RE, Emiliani S, Nakayama K, Castro A, Labbé JC, Lorca T, Nakayama Ki K, Benkirane M . Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome . Molecular and Cellular Biology . 21 . 23 . 7956–70 . December 2001 . 11689688 . 99964 . 10.1128/MCB.21.23.7956-7970.2001 .