CDC27 explained

Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene.^{[1] [2]}

Function

The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizosaccharomyces pombe nuc 2. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eucaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and thus may be involved in controlling the timing of mitosis.

Interactions

CDC27 has been shown to interact with:

• ANAPC10,
• ANAPC11,
• ANAPC1,^{[3] [4]}
• ANAPC4,^{[3] [5]}
• ANAPC5,^{[3] [5] [6]}
• ANAPC7,^{[3] [5]}
• CDC16,^{[3] [5] [7]}
• CDC20,^{[3] [8] [9] [10] [11] [12]}
• CDC23,^{[3] [5]}
• CDH1,^[3]
• FZR1,^{[13] [14]}
• MAD2L1^{[8] [11]} and
• PIN1.^{[15] [16]}

Further reading

• Tugendreich S, Tomkiel J, Earnshaw W, Hieter P . CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition . Cell . 81 . 2 . 261–8 . Apr 1995 . 7736578 . 10.1016/0092-8674(95)90336-4 . 17907584 . free .
• Chen PL, Ueng YC, Durfee T, Chen KC, Yang-Feng T, Lee WH . Identification of a human homologue of yeast nuc2 which interacts with the retinoblastoma protein in a specific manner . Cell Growth & Differentiation . 6 . 2 . 199–210 . Feb 1995 . 7756179 .
• Ho PP, Couch FJ, Brody LC, Abel KJ, Boehnke M, Shearon TH, Chandrasekharappa SC, Collins FS, Weber BL . Localization of the human homolog of the yeast cell division control 27 gene (CDC27) proximal to ITGB3 on human chromosome 17q21.3 . Somatic Cell and Molecular Genetics . 21 . 5 . 351–5 . Sep 1995 . 8619132 . 10.1007/BF02257470 . 2027.42/45546 . 9614052 . free .
• Ollendorff V, Donoghue DJ . The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex . The Journal of Biological Chemistry . 272 . 51 . 32011–8 . Dec 1997 . 9405394 . 10.1074/jbc.272.51.32011 . free .
• Yu H, Peters JM, King RW, Page AM, Hieter P, Kirschner MW . Identification of a cullin homology region in a subunit of the anaphase-promoting complex . Science . 279 . 5354 . 1219–22 . Feb 1998 . 9469815 . 10.1126/science.279.5354.1219 . 1998Sci...279.1219Y .
• Shen M, Stukenberg PT, Kirschner MW, Lu KP . The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins . Genes & Development . 12 . 5 . 706–20 . Mar 1998 . 9499405 . 316589 . 10.1101/gad.12.5.706 .
• Zhou BB, Li H, Yuan J, Kirschner MW . Caspase-dependent activation of cyclin-dependent kinases during Fas-induced apoptosis in Jurkat cells . Proceedings of the National Academy of Sciences of the United States of America . 95 . 12 . 6785–90 . Jun 1998 . 9618490 . 22635 . 10.1073/pnas.95.12.6785 . 1998PNAS...95.6785Z . free .
• Wassmann K, Benezra R . Mad2 transiently associates with an APC/p55Cdc complex during mitosis . Proceedings of the National Academy of Sciences of the United States of America . 95 . 19 . 11193–8 . Sep 1998 . 9736712 . 21618 . 10.1073/pnas.95.19.11193 . 1998PNAS...9511193W . free .
• Lu PJ, Zhou XZ, Shen M, Lu KP . Function of WW domains as phosphoserine- or phosphothreonine-binding modules . Science . 283 . 5406 . 1325–8 . Feb 1999 . 10037602 . 10.1126/science.283.5406.1325 . 1999Sci...283.1325L .
• Grossberger R, Gieffers C, Zachariae W, Podtelejnikov AV, Schleiffer A, Nasmyth K, Mann M, Peters JM . Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex . The Journal of Biological Chemistry . 274 . 20 . 14500–7 . May 1999 . 10318877 . 10.1074/jbc.274.20.14500 . free .
• Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ . Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC . The Journal of Cell Biology . 146 . 5 . 941–54 . Sep 1999 . 10477750 . 2169490 . 10.1083/jcb.146.5.941 .
• Gieffers C, Peters BH, Kramer ER, Dotti CG, Peters JM . Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons . Proceedings of the National Academy of Sciences of the United States of America . 96 . 20 . 11317–22 . Sep 1999 . 10500174 . 18031 . 10.1073/pnas.96.20.11317 . 1999PNAS...9611317G . free .
• Gmachl M, Gieffers C, Podtelejnikov AV, Mann M, Peters JM . The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex . Proceedings of the National Academy of Sciences of the United States of America . 97 . 16 . 8973–8 . Aug 2000 . 10922056 . 16806 . 10.1073/pnas.97.16.8973 . 2000PNAS...97.8973G . free .
• Rippmann JF, Hobbie S, Daiber C, Guilliard B, Bauer M, Birk J, Nar H, Garin-Chesa P, Rettig WJ, Schnapp A . Phosphorylation-dependent proline isomerization catalyzed by Pin1 is essential for tumor cell survival and entry into mitosis . Cell Growth & Differentiation . 11 . 7 . 409–16 . Jul 2000 . 10939594 .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Reports . 1 . 3 . 287–92 . Sep 2000 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Wendt KS, Vodermaier HC, Jacob U, Gieffers C, Gmachl M, Peters JM, Huber R, Sondermann P . Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex . Nature Structural Biology . 8 . 9 . 784–8 . Sep 2001 . 11524682 . 10.1038/nsb0901-784 . 27021761 .
• Stroschein SL, Bonni S, Wrana JL, Luo K . Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN . Genes & Development . 15 . 21 . 2822–36 . Nov 2001 . 11691834 . 312804 . 10.1101/gad.912901 .
• Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ . Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells . The Journal of Cell Biology . 158 . 5 . 841–7 . Sep 2002 . 12196507 . 2173153 . 10.1083/jcb.200201135 .
• Topper LM, Campbell MS, Tugendreich S, Daum JR, Burke DJ, Hieter P, Gorbsky GJ . The dephosphorylated form of the anaphase-promoting complex protein Cdc27/Apc3 concentrates on kinetochores and chromosome arms in mitosis . Cell Cycle . 1 . 4 . 282–92 . 2002 . 12429948 . 10.4161/cc.1.4.139 . 10799434 .

Notes and References

1. Tugendreich S, Boguski MS, Seldin MS, Hieter P . Linking yeast genetics to mammalian genomes: identification and mapping of the human homolog of CDC27 via the expressed sequence tag (EST) data base . Proceedings of the National Academy of Sciences of the United States of America . 90 . 21 . 10031–5 . Nov 1993 . 8234252 . 47707 . 10.1073/pnas.90.21.10031 . 1993PNAS...9010031T . free .
2. Web site: Entrez Gene: CDC27 cell division cycle 27 homolog (S. cerevisiae).
3. Vodermaier HC, Gieffers C, Maurer-Stroh S, Eisenhaber F, Peters JM . TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1 . Current Biology . 13 . 17 . 1459–68 . Sep 2003 . 12956947 . 10.1016/s0960-9822(03)00581-5. 5942532 . free . 2003CBio...13.1459V .
4. Sumara I, Vorlaufer E, Gieffers C, Peters BH, Peters JM . Characterization of vertebrate cohesin complexes and their regulation in prophase . The Journal of Cell Biology . 151 . 4 . 749–62 . Nov 2000 . 11076961 . 2169443 . 10.1083/jcb.151.4.749.
5. Gmachl M, Gieffers C, Podtelejnikov AV, Mann M, Peters JM . The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex . Proceedings of the National Academy of Sciences of the United States of America . 97 . 16 . 8973–8 . Aug 2000 . 10922056 . 16806 . 10.1073/pnas.97.16.8973. 2000PNAS...97.8973G . free .
6. Koloteva-Levine N, Pinchasi D, Pereman I, Zur A, Brandeis M, Elroy-Stein O . The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ribosome entry site-mediated translation . Molecular and Cellular Biology . 24 . 9 . 3577–87 . May 2004 . 15082755 . 387753 . 10.1128/mcb.24.9.3577-3587.2004.
7. Ollendorff V, Donoghue DJ . The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex . The Journal of Biological Chemistry . 272 . 51 . 32011–8 . Dec 1997 . 9405394 . 10.1074/jbc.272.51.32011. free .
8. Kallio M, Weinstein J, Daum JR, Burke DJ, Gorbsky GJ . Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events . The Journal of Cell Biology . 141 . 6 . 1393–406 . Jun 1998 . 9628895 . 2132789 . 10.1083/jcb.141.6.1393.
9. D'Angiolella V, Mari C, Nocera D, Rametti L, Grieco D . The spindle checkpoint requires cyclin-dependent kinase activity . Genes & Development . 17 . 20 . 2520–5 . Oct 2003 . 14561775 . 218146 . 10.1101/gad.267603 .
10. Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ . Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells . The Journal of Cell Biology . 158 . 5 . 841–7 . Sep 2002 . 12196507 . 2173153 . 10.1083/jcb.200201135 .
11. Wassmann K, Benezra R . Mad2 transiently associates with an APC/p55Cdc complex during mitosis . Proceedings of the National Academy of Sciences of the United States of America . 95 . 19 . 11193–8 . Sep 1998 . 9736712 . 21618 . 10.1073/pnas.95.19.11193. 1998PNAS...9511193W . free .
12. Nilsson J, Yekezare M, Minshull J, Pines J . The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction . Nature Cell Biology . 10 . 12 . 1411–20 . Dec 2008 . 18997788 . 2635557 . 10.1038/ncb1799 .
13. Kramer ER, Gieffers C, Hölzl G, Hengstschläger M, Peters JM . Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family . Current Biology . 8 . 22 . 1207–10 . Nov 1998 . 9811605 . 10.1016/s0960-9822(07)00510-6. 17181162 . free . 1998CBio....8.1207K .
14. Zhou Y, Ching YP, Ng RW, Jin DY . Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1 . The Biochemical Journal . 374 . Pt 2 . 349–58 . Sep 2003 . 12797865 . 1223613 . 10.1042/BJ20030600 .
15. Shen M, Stukenberg PT, Kirschner MW, Lu KP . The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins . Genes & Development . 12 . 5 . 706–20 . Mar 1998 . 9499405 . 316589 . 10.1101/gad.12.5.706.
16. Lu PJ, Zhou XZ, Shen M, Lu KP . Function of WW domains as phosphoserine- or phosphothreonine-binding modules . Science . 283 . 5406 . 1325–8 . Feb 1999 . 10037602 . 10.1126/science.283.5406.1325. 1999Sci...283.1325L .