SIAH1 explained

E3 ubiquitin-protein ligase SIAH1 is an enzyme that in humans is encoded by the SIAH1 gene.^{[1] [2]}

Function

This gene encodes for a polypeptide structure that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.^[3]

Interactions

SIAH1 has been shown to interact with:

• APC,^[4]
• BAG1,^[5]
• CACYBP,^[6]
• KHDRBS3,^{[7] [8]}
• KIF22,^[9]
• NUMB,^[10]
• PEG10,^[11]
• PEG3^[12]
• POU2AF1,^[13]
• RBBP8,^[14] and
• TRIB3.^[15]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Nemani M, Linares-Cruz G, Bruzzoni-Giovanelli H, Roperch JP, Tuynder M, Bougueleret L, Cherif D, Medhioub M, Pasturaud P, Alvaro V, der Sarkissan H, Cazes L, Le Paslier D, Le Gall I, Israeli D, Dausset J, Sigaux F, Chumakov I, Oren M, Calvo F, Amson RB, Cohen D, Telerman A . Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression . Proceedings of the National Academy of Sciences of the United States of America . 93 . 17 . 9039–42 . August 1996 . 8799150 . 38591 . 10.1073/pnas.93.17.9039 . 1996PNAS...93.9039N . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Block KL, Vornlocher HP, Hershey JW . Characterization of cDNAs encoding the p44 and p35 subunits of human translation initiation factor eIF3 . The Journal of Biological Chemistry . 273 . 48 . 31901–8 . November 1998 . 9822659 . 10.1074/jbc.273.48.31901 . free .
• Hu G, Fearon ER . Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins . Molecular and Cellular Biology . 19 . 1 . 724–32 . January 1999 . 9858595 . 83929 . 10.1128/mcb.19.1.724.
• Tanikawa J, Ichikawa-Iwata E, Kanei-Ishii C, Nakai A, Matsuzawa S, Reed JC, Ishii S . p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3 . The Journal of Biological Chemistry . 275 . 20 . 15578–85 . May 2000 . 10747903 . 10.1074/jbc.M000372200 . free .
• Medhioub M, Vaury C, Hamelin R, Thomas G . Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene . International Journal of Cancer . 87 . 6 . 794–7 . September 2000 . 10956387 . 10.1002/1097-0215(20000915)87:6<794::AID-IJC5>3.0.CO;2-B . free .
• Matsuzawa SI, Reed JC . Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses . Molecular Cell . 7 . 5 . 915–26 . May 2001 . 11389839 . 10.1016/S1097-2765(01)00242-8 . free .
• Boehm J, He Y, Greiner A, Staudt L, Wirth T . Regulation of BOB.1/OBF.1 stability by SIAH . The EMBO Journal . 20 . 15 . 4153–62 . August 2001 . 11483518 . 149152 . 10.1093/emboj/20.15.4153 .
• Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L . Regulation of synaptophysin degradation by mammalian homologues of seven in absentia . The Journal of Biological Chemistry . 277 . 12 . 10273–82 . March 2002 . 11786535 . 10.1074/jbc.M107857200 . free .
• Maeda A, Yoshida T, Kusuzaki K, Sakai T . The characterization of the human Siah-1 promoter(1) . FEBS Letters . 512 . 1–3 . 223–6 . February 2002 . 11852084 . 10.1016/S0014-5793(02)02265-2 . 24436936 . free .
• Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, Navaratnam N . An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22 . Genomics . 79 . 3 . 285–96 . March 2002 . 11863358 . 10.1006/geno.2002.6718 .

Notes and References

1. Hu G, Chung YL, Glover T, Valentine V, Look AT, Fearon ER . Characterization of human homologs of the Drosophila seven in absentia (sina) gene . Genomics . 46 . 1 . 103–11 . November 1997 . 9403064 . 10.1006/geno.1997.4997 . free .
2. Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER . Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway . Genes & Development . 11 . 20 . 2701–14 . October 1997 . 9334332 . 316613 . 10.1101/gad.11.20.2701 .
3. Web site: Entrez Gene: SIAH1 seven in absentia homolog 1 (Drosophila).
4. Liu J, Stevens J, Rote CA, Yost HJ, Hu Y, Neufeld KL, White RL, Matsunami N . Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein . Molecular Cell . 7 . 5 . 927–36 . May 2001 . 11389840 . 10.1016/S1097-2765(01)00241-6 . free .
5. Matsuzawa S, Takayama S, Froesch BA, Zapata JM, Reed JC . p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1 . The EMBO Journal . 17 . 10 . 2736–47 . May 1998 . 9582267 . 1170614 . 10.1093/emboj/17.10.2736 .
6. Matsuzawa SI, Reed JC . Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses . Molecular Cell . 7 . 5 . 915–26 . May 2001 . 11389839 . 10.1016/S1097-2765(01)00242-8 . free .
7. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
8. Venables JP, Dalgliesh C, Paronetto MP, Skitt L, Thornton JK, Saunders PT, Sette C, Jones KT, Elliott DJ . SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome . Human Molecular Genetics . 13 . 14 . 1525–34 . July 2004 . 15163637 . 10.1093/hmg/ddh165 . free .
9. Germani A, Bruzzoni-Giovanelli H, Fellous A, Gisselbrecht S, Varin-Blank N, Calvo F . SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis . Oncogene . 19 . 52 . 5997–6006 . December 2000 . 11146551 . 10.1038/sj.onc.1204002 . free .
10. Susini L, Passer BJ, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron MC, Israël A, Amson R, Oren M, Telerman A . Siah-1 binds and regulates the function of Numb . Proceedings of the National Academy of Sciences of the United States of America . 98 . 26 . 15067–72 . December 2001 . 11752454 . 64984 . 10.1073/pnas.261571998 . 2001PNAS...9815067S . Laurent Susini . free .
11. Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y . Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1 . Cancer Research . 63 . 12 . 3043–8 . June 2003 . 12810624 .
12. Relaix F, ((Wei Xj)), Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X . Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis . Proceedings of the National Academy of Sciences of the United States of America . 97 . 5 . 2105–10 . February 2000 . 10681424 . 15761 . 10.1073/pnas.040378897 . 2000PNAS...97.2105R . free .
13. Tiedt R, Bartholdy BA, Matthias G, Newell JW, Matthias P . The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1 . The EMBO Journal . 20 . 15 . 4143–52 . August 2001 . 11483517 . 149178 . 10.1093/emboj/20.15.4143 .
14. Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H . SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway . Oncogene . 22 . 55 . 8845–51 . December 2003 . 14654780 . 10.1038/sj.onc.1206994 . free .
15. Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F . E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3 . Cellular Signalling . 20 . 5 . 942–8 . May 2008 . 18276110 . 10.1016/j.cellsig.2008.01.010 .