MAD2L1 explained

Mitotic spindle assembly checkpoint protein MAD2A is a protein that in humans is encoded by the MAD2L1 gene.^{[1] [2] [3]}

Function

MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is related to the MAD2L2 gene located on chromosome 1. A MAD2 pseudogene has been mapped to chromosome 14.^[3]

Interactions

MAD2L1 has been shown to interact with:

• ADAM17,^{[4] [5]}
• BUB1B,^[6]
• CDC20,^{[7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]}
• CDC27^{[13] [14]} and
• Estrogen receptor beta,^[19]
• MAD2L2,^[20]
• Mad1,^{[10] [20] [21]} and
• UBD.^[22]

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 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• O'Neill TJ, Zhu Y, Gustafson TA . Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation . J. Biol. Chem. . 272 . 15 . 10035–40 . 1997 . 9092546 . 10.1074/jbc.272.15.10035 . 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 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Jin DY, Spencer F, Jeang KT . Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1 . Cell . 93 . 1 . 81–91 . 1998 . 9546394 . 10.1016/S0092-8674(00)81148-4 . 7345931 . free .
• Krishnan R, Goodman B, Jin DY, Jeang KT, Collins C, Stetten G, Spencer F . Map location and gene structure of the Homo sapiens mitotic arrest deficient 2 (MAD2L1) gene at 4q27 . Genomics . 49 . 3 . 475–8 . 1998 . 9615237 . 10.1006/geno.1998.5233 . free .
• 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 . J. Cell Biol. . 141 . 6 . 1393–406 . 1998 . 9628895 . 2132789 . 10.1083/jcb.141.6.1393 .
• Fang G, Yu H, Kirschner MW . The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation . Genes Dev. . 12 . 12 . 1871–83 . 1998 . 9637688 . 316912 . 10.1101/gad.12.12.1871 .
• Wassmann K, Benezra R . Mad2 transiently associates with an APC/p55Cdc complex during mitosis . Proc. Natl. Acad. Sci. U.S.A. . 95 . 19 . 11193–8 . 1998 . 9736712 . 21618 . 10.1073/pnas.95.19.11193 . 1998PNAS...9511193W . free .
• Liu YC, Pan J, Zhang C, Fan W, Collinge M, Bender JR, Weissman SM . A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2 . Proc. Natl. Acad. Sci. U.S.A. . 96 . 8 . 4313–8 . 1999 . 10200259 . 16329 . 10.1073/pnas.96.8.4313 . 1999PNAS...96.4313L . free .
• Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C . Characterization of MAD2B and other mitotic spindle checkpoint genes . Genomics . 58 . 2 . 181–7 . 1999 . 10366450 . 10.1006/geno.1999.5831 . free .
• Nelson KK, Schlöndorff J, Blobel CP . Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2beta . Biochem. J. . 343 . 3. 673–80 . 1999 . 10527948 . 1220601 . 10.1042/0264-6021:3430673 .
• Murakumo Y, Roth T, Ishii H, Rasio D, Numata S, Croce CM, Fishel R . A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2 . J. Biol. Chem. . 275 . 6 . 4391–7 . 2000 . 10660610 . 10.1074/jbc.275.6.4391 . free .
• Luo X, Fang G, Coldiron M, Lin Y, Yu H, Kirschner MW, Wagner G . Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20 . Nat. Struct. Biol. . 7 . 3 . 224–9 . 2000 . 10700282 . 10.1038/73338 . 1721494 .
• Poelzl G, Kasai Y, Mochizuki N, Shaul PW, Brown M, Mendelsohn ME . Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2 . Proc. Natl. Acad. Sci. U.S.A. . 97 . 6 . 2836–9 . 2000 . 10706629 . 16016 . 10.1073/pnas.050580997 . 2000PNAS...97.2836P . free .
• Steuerwald N, Cohen J, Herrera RJ, Sandalinas M, Brenner CA . Association between spindle assembly checkpoint expression and maternal age in human oocytes . Mol. Hum. Reprod. . 7 . 1 . 49–55 . 2001 . 11134360 . 10.1093/molehr/7.1.49 . free .
• Campbell MS, Chan GK, Yen TJ . Mitotic checkpoint proteins HsMAD1 and HsMAD2 are associated with nuclear pore complexes in interphase . J. Cell Sci. . 114 . Pt 5 . 953–63 . 2001 . 10.1242/jcs.114.5.953 . 11181178 . free .
• Zhang Y, Lees E . Identification of an overlapping binding domain on Cdc20 for Mad2 and anaphase-promoting complex: model for spindle checkpoint regulation . Mol. Cell. Biol. . 21 . 15 . 5190–9 . 2001 . 11438673 . 87243 . 10.1128/MCB.21.15.5190-5199.2001 .
• Sudakin V, Chan GK, Yen TJ . Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 . J. Cell Biol. . 154 . 5 . 925–36 . 2001 . 11535616 . 2196190 . 10.1083/jcb.200102093 .

Notes and References

1. Li Y, Benezra R . Identification of a human mitotic checkpoint gene: hsMAD2 . Science . 274 . 5285 . 246–8 . October 1996 . 8824189 . 10.1126/science.274.5285.246 . 1996Sci...274..246L . 41334564 .
2. Xu L, Deng HX, Yang Y, Xia JH, Hung WY, Siddque T . Assignment of mitotic arrest deficient protein 2 (MAD2L1) to human chromosome band 5q23.3 by in situ hybridization . Cytogenet. Cell Genet. . 78 . 1 . 63–4 . November 1997 . 9345911 . 10.1159/000134631 .
3. Web site: Entrez Gene: MAD2L1 MAD2 mitotic arrest deficient-like 1 (yeast).
4. Nelson KK, Schlöndorff J, Blobel CP . Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2beta . Biochem. J. . 343 . 3. 673–80 . November 1999 . 10527948 . 1220601 . 10.1042/0264-6021:3430673.
5. Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR . Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases . J. Biol. Chem. . 277 . 7 . 4999–5007 . February 2002 . 11741929 . 10.1074/jbc.M107430200 . free .
6. Sudakin V, Chan GK, Yen TJ . Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 . J. Cell Biol. . 154 . 5 . 925–36 . September 2001 . 11535616 . 2196190 . 10.1083/jcb.200102093 .
7. Zhang Y, Lees E . Identification of an overlapping binding domain on Cdc20 for Mad2 and anaphase-promoting complex: model for spindle checkpoint regulation . Mol. Cell. Biol. . 21 . 15 . 5190–9 . August 2001 . 11438673 . 87243 . 10.1128/MCB.21.15.5190-5199.2001 .
8. Sihn CR, Suh EJ, Lee KH, Kim TY, Kim SH . p55CDC/hCDC20 mutant induces mitotic catastrophe by inhibiting the MAD2-dependent spindle checkpoint activity in tumor cells . Cancer Lett. . 201 . 2 . 203–10 . November 2003 . 14607335 . 10.1016/s0304-3835(03)00465-8.
9. Luo X, Fang G, Coldiron M, Lin Y, Yu H, Kirschner MW, Wagner G . Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20 . Nat. Struct. Biol. . 7 . 3 . 224–9 . March 2000 . 10700282 . 10.1038/73338 . 1721494 .
10. Sironi L, Melixetian M, Faretta M, Prosperini E, Helin K, Musacchio A . Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint . EMBO J. . 20 . 22 . 6371–82 . November 2001 . 11707408 . 125308 . 10.1093/emboj/20.22.6371 .
11. D'Angiolella V, Mari C, Nocera D, Rametti L, Grieco D . The spindle checkpoint requires cyclin-dependent kinase activity . Genes Dev. . 17 . 20 . 2520–5 . October 2003 . 14561775 . 218146 . 10.1101/gad.267603 .
12. Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ . Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells . J. Cell Biol. . 158 . 5 . 841–7 . September 2002 . 12196507 . 2173153 . 10.1083/jcb.200201135 .
13. Wassmann K, Benezra R . Mad2 transiently associates with an APC/p55Cdc complex during mitosis . Proc. Natl. Acad. Sci. U.S.A. . 95 . 19 . 11193–8 . September 1998 . 9736712 . 21618 . 10.1073/pnas.95.19.11193. 1998PNAS...9511193W . free .
14. 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 . J. Cell Biol. . 141 . 6 . 1393–406 . June 1998 . 9628895 . 2132789 . 10.1083/jcb.141.6.1393.
15. Fang G, Yu H, Kirschner MW . The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation . Genes Dev. . 12 . 12 . 1871–83 . June 1998 . 9637688 . 316912 . 10.1101/gad.12.12.1871.
16. Skoufias DA, Andreassen PR, Lacroix FB, Wilson L, Margolis RL . Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints . Proc. Natl. Acad. Sci. U.S.A. . 98 . 8 . 4492–7 . April 2001 . 11274370 . 31862 . 10.1073/pnas.081076898 . 2001PNAS...98.4492S . free .
17. Nilsson J, Yekezare M, Minshull J, Pines J . The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction . Nat. Cell Biol. . 10 . 12 . 1411–20 . December 2008 . 18997788 . 2635557 . 10.1038/ncb1799 .
18. Privette LM, Weier JF, Nguyen HN, Yu X, Petty EM . Loss of CHFR in human mammary epithelial cells causes genomic instability by disrupting the mitotic spindle assembly checkpoint . Neoplasia . 10 . 7 . 643–52 . July 2008 . 18592005 . 2435002 . 10.1593/neo.08176.
19. Poelzl G, Kasai Y, Mochizuki N, Shaul PW, Brown M, Mendelsohn ME . Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2 . Proc. Natl. Acad. Sci. U.S.A. . 97 . 6 . 2836–9 . March 2000 . 10706629 . 16016 . 10.1073/pnas.050580997 . 2000PNAS...97.2836P . free .
20. Murakumo Y, Roth T, Ishii H, Rasio D, Numata S, Croce CM, Fishel R . A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2 . J. Biol. Chem. . 275 . 6 . 4391–7 . February 2000 . 10660610 . 10.1074/jbc.275.6.4391. free .
21. 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 . 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 .
22. Liu YC, Pan J, Zhang C, Fan W, Collinge M, Bender JR, Weissman SM . A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2 . Proc. Natl. Acad. Sci. U.S.A. . 96 . 8 . 4313–8 . April 1999 . 10200259 . 16329 . 10.1073/pnas.96.8.4313. 1999PNAS...96.4313L . free .