40S ribosomal protein S27 explained

40S ribosomal protein S27, also known as metallopan-stimulin 1 or MPS-1, is a protein that in humans is encoded by the RPS27 gene.^{[1] [2] [3]} Metallopanstimulin is a zinc finger protein proposed to be involved DNA repair as well as oncogenesis.^[4]

Function

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S27E family of ribosomal proteins. It contains a C4-type zinc finger domain that can bind to zinc. The encoded protein has been shown to be able to bind to nucleic acid. It is located in the cytoplasm as a ribosomal component, but it has also been detected in the nucleus. Studies in rat indicate that ribosomal protein S27 is located near ribosomal protein S18 in the 40S subunit and is covalently linked to translation initiation factor eIF3. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.^[3]

Clinical significance

Its expression is increased in several types of malignancy and MPS levels have been reported to drop with treatment of some cancers. It has also been used as a target for some chemotherapies, which aim to chelate out the zinc from the zinc finger motif of the MPS, thus yielding it inactive. These therapies have shown promise for the treatment of cancer in laboratory experiments and some limited clinical trials. Head and neck cancer transfected to overexpress this protein have demonstrated suppressed growth.^[4]

Further reading

• Scurry WC, Stack BC . Role of metalloproteins in the clinical management of head and neck squamous cell carcinoma . Head & Neck . 29 . 12 . 1144–55 . Dec 2007 . 17657798 . 10.1002/hed.20655 . 10.1.1.610.1189 . 11534394 .
• Stack BC, Hollenbeak CS, Lee CM, Dunphy FR, Lowe VJ, Hamilton PD . Metallopanstimulin as a marker for head and neck cancer . World Journal of Surgical Oncology . 2 . 45 . December 2004 . 15598348 . 544581 . 10.1186/1477-7819-2-45 . free .
• Lee WJ, Keefer K, Hollenbeak CS, Stack BC . A new assay to screen for head and neck squamous cell carcinoma using the tumor marker metallopanstimulin . Otolaryngology–Head and Neck Surgery . 131 . 4 . 466–71 . Oct 2004 . 15467619 . 10.1016/j.otohns.2004.03.011 . 22629299 .
• Wool IG, Chan YL, Glück A . Structure and evolution of mammalian ribosomal proteins . Biochemistry and Cell Biology . 73 . 11–12 . 933–47 . 1996 . 8722009 . 10.1139/o95-101 .
• Fernandez-Pol JA, Klos DJ, Hamilton PD . Metallopanstimulin gene product produced in a baculovirus expression system is a nuclear phosphoprotein that binds to DNA . Cell Growth & Differentiation . 5 . 8 . 811–25 . Aug 1994 . 7986747 .
• Vladimirov SN, Ivanov AV, Karpova GG, Musolyamov AK, Egorov TA, Thiede B, Wittmann-Liebold B, Otto A . Characterization of the human small-ribosomal-subunit proteins by N-terminal and internal sequencing, and mass spectrometry . European Journal of Biochemistry . 239 . 1 . 144–9 . Jul 1996 . 8706699 . 10.1111/j.1432-1033.1996.0144u.x . free .
• Kenmochi N, Kawaguchi T, Rozen S, Davis E, Goodman N, Hudson TJ, Tanaka T, Page DC . A map of 75 human ribosomal protein genes . Genome Research . 8 . 5 . 509–23 . May 1998 . 9582194 . 10.1101/gr.8.5.509 . free .
• Yoshihama M, Uechi T, Asakawa S, Kawasaki K, Kato S, Higa S, Maeda N, Minoshima S, Tanaka T, Shimizu N, Kenmochi N . The human ribosomal protein genes: sequencing and comparative analysis of 73 genes . Genome Research . 12 . 3 . 379–90 . Mar 2002 . 11875025 . 155282 . 10.1101/gr.214202 .
• Atsuta Y, Aoki N, Sato K, Oikawa K, Nochi H, Miyokawa N, Hirata S, Kimura S, Sasajima T, Katagiri M . Identification of metallopanstimulin-1 as a member of a tumor associated antigen in patients with breast cancer . Cancer Letters . 182 . 1 . 101–7 . Aug 2002 . 12175529 . 10.1016/S0304-3835(02)00068-X .
• Martin-Lluesma S, Stucke VM, Nigg EA . Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2 . Science . 297 . 5590 . 2267–70 . Sep 2002 . 12351790 . 10.1126/science.1075596 . 2002Sci...297.2267M . 7879023 .
• Liu ST, Chan GK, Hittle JC, Fujii G, Lees E, Yen TJ . Human MPS1 kinase is required for mitotic arrest induced by the loss of CENP-E from kinetochores . Molecular Biology of the Cell . 14 . 4 . 1638–51 . Apr 2003 . 12686615 . 153128 . 10.1091/mbc.02-05-0074 .
• Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway . Nature Cell Biology . 6 . 2 . 97–105 . Feb 2004 . 14743216 . 10.1038/ncb1086 . 11683986 .
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M . Nucleolar proteome dynamics . Nature . 433 . 7021 . 77–83 . Jan 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 .
• Yu Y, Ji H, Doudna JA, Leary JA . Mass spectrometric analysis of the human 40S ribosomal subunit: native and HCV IRES-bound complexes . Protein Science . 14 . 6 . 1438–46 . Jun 2005 . 15883184 . 2253395 . 10.1110/ps.041293005 .
• 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 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Bhonde MR, Hanski ML, Budczies J, Cao M, Gillissen B, Moorthy D, Simonetta F, Scherübl H, Truss M, Hagemeier C, Mewes HW, Daniel PT, Zeitz M, Hanski C . DNA damage-induced expression of p53 suppresses mitotic checkpoint kinase hMps1: the lack of this suppression in p53MUT cells contributes to apoptosis . The Journal of Biological Chemistry . 281 . 13 . 8675–85 . Mar 2006 . 16446370 . 10.1074/jbc.M511333200 . free .
• Wang YW, Qu Y, Li JF, Chen XH, Liu BY, Gu QL, Zhu ZG . In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity . Clinical Cancer Research . 12 . 16 . 4965–73 . Aug 2006 . 16914586 . 10.1158/1078-0432.CCR-05-2316 . free .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . Nov 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .

Notes and References

1. Tsui SK, Lee SM, Fung KP, Waye MM, Lee CY . Primary structures and sequence analysis of human ribosomal proteins L39 and S27 . Biochemistry and Molecular Biology International . 40 . 3 . 611–6 . Oct 1996 . 8908372 . 10.1080/15216549600201203 . 7909023 . free .
2. Fernandez-Pol JA, Klos DJ, Hamilton PD . A growth factor-inducible gene encodes a novel nuclear protein with zinc finger structure . The Journal of Biological Chemistry . 268 . 28 . 21198–204 . Oct 1993 . 10.1016/S0021-9258(19)36910-8 . 8407955 . free .
3. Web site: Entrez Gene: RPS27 ribosomal protein S27 (metallopanstimulin 1).
4. Fernandez-Pol JA . Metallopanstimulin as a novel tumor marker in sera of patients with various types of common cancers: implications for prevention and therapy . Anticancer Research . 16 . 4B . 2177–85 . 1996 . 8694540 .