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Licensed Unlicensed Requires Authentication Published by De Gruyter June 26, 2006

Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?

  • Olivia L. Tan , Astrid K. Whitbread , Judith A. Clements and Ying Dong
From the journal Biological Chemistry

Abstract

The kallikrein-related peptidase (KLK) gene family of 15 serine proteases encodes many proteins, including prostate specific antigen (PSA or KLK3), that are well described and/or are potential biomarkers for hormone-related cancers. Variant mRNA transcripts produced by alternative splicing, polyadenylation or AUG sites, or intron retention have been found for each of the KLK genes. The predicted protein for many of these alternative transcripts is different from that of the classical kallikrein-related peptidases and would not be an active serine protease. The majority of these novel protein isoforms have not been studied in vivo. The possible function(s) of the variant transcripts/protein isoforms and potential roles that they may play in hormone-related cancers are still unknown and are the focus of this short review.

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Corresponding author

References

Beaudoing, E., Freier, S., Wyatt, J.R., Claverie, J.M., and Gautheret, D. (2000). Patterns of variant polyadenylation signal usage in human genes. Genome Res.10, 1001–1010.10.1101/gr.10.7.1001Search in Google Scholar

Bharaj, B.B., Luo, L.Y., Jung, K., Stephan, C., and Diamandis, E.P. (2002). Identification of single nucleotide polymorphisms in the human kallikrein 10 (KLK10) gene and their association with prostate, breast, testicular, and ovarian cancers. Prostate51, 35–41.10.1002/pros.10076Search in Google Scholar

Black, D.L. (2000). Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell103, 367–370.10.1016/S0092-8674(00)00128-8Search in Google Scholar

Black, M.H., Giai, M., Ponzone, R., Sismondi, P., Yu, H., and Diamandis, E.P. (2000). Serum total and free prostate-specific antigen for breast cancer diagnosis in women. Clin. Cancer Res.6, 467–473.Search in Google Scholar

Borgono, C.A. and Diamandis, E.P. (2004). The emerging roles of human tissue kallikreins in cancer. Nat. Rev. Cancer4, 876–890.10.1038/nrc1474Search in Google Scholar PubMed

Chang, A., Yousef, G.M., Jung, K., Rajpert-De Meyts, E., and Diamandis, E.P. (2001). Identification and molecular characterization of five novel kallikrein gene 13 (KLK13; KLK-L4) splice variants: differential expression in the human testis and testicular cancer. Anticancer Res.21, 3147–3152.Search in Google Scholar

Chen, L.M., Murray, S.R., Chai, K.X., Chao, L., and Chao, J. (1994). Molecular cloning and characterization of a novel kallikrein transcript in colon and its distribution in human tissues. Braz. J. Med. Biol. Res.27, 1829–1838.Search in Google Scholar

Christophi, G.P., Isackson, P.J., Blaber, S., Blaber, M., Rodriguez, M., and Scarisbrick, I.A. (2004). Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease. J. Neurochem.91, 1439–1449.10.1111/j.1471-4159.2004.02826.xSearch in Google Scholar PubMed

Clements, J.A., Willemsen, N.M., Myers, S.A., and Dong, Y. (2004). The tissue kallikrein family of serine proteases: functional roles in human disease and potential as clinical biomarkers. Crit. Rev. Clin. Lab. Sci.41, 265–312.10.1080/10408360490471931Search in Google Scholar PubMed

David, A., Mabjeesh, N., Azar, I., Biton, S., Engel, S., Bernstein, J., Romano, J., Avidor, Y., Waks, T., Eshhar, Z., et al. (2002). Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 gives rise to novel prostate-specific proteins. J. Biol. Chem.277, 18084–18090.10.1074/jbc.M102285200Search in Google Scholar PubMed

Ding, W.Q., Kuntz, S., Bohmig, M., Wiedenmann, B., and Miller, L.J. (2002). Dominant negative action of an abnormal secretin receptor arising from mRNA missplicing in a gastrinoma. Gastroenterology122, 500–511.10.1053/gast.2002.31039Search in Google Scholar PubMed

Dong, Y., Kaushal, A., Bui, L., Chu, S., Fuller, P.J., Nicklin, J., Samaratunga, H., and Clements, J.A. (2001). Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. Clin. Cancer Res.7, 2363–2371.Search in Google Scholar

Dong, Y., Kaushal, A., Brattsand, M., Nicklin, J., and Clements, J.A. (2003). Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. Clin. Cancer Res.9, 1710–1720.Search in Google Scholar

Dong, Y., Bui, L., Odorico, D.M., Tan, O.L., Myers, S.A., Samaratunga, H., Gardiner, R.A., and Clements, J.A. (2005). Compartmentalised expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. Endocr. Relat. Cancer12, 875–889.10.1677/erc.1.01062Search in Google Scholar PubMed

Faustino, N.A., and Cooper, T.A. (2003). Pre-mRNA splicing and human disease. Genes Dev.17, 419–437.10.1101/gad.1048803Search in Google Scholar PubMed

Fiordalisi, J.J., Holly, S.P., Johnson, R.L. II, Parise, L.V., and Cox, A.D. (2002). A distinct class of dominant negative Ras mutants: cytosolic GTP-bound Ras effector domain mutants that inhibit Ras signaling and transformation and enhance cell adhesion. J. Biol. Chem.277, 10813–10823.10.1074/jbc.M107684200Search in Google Scholar

Fortier, A.H., Nelson, B.J., Grella, D.K., and Holaday, J.W. (1999). Antiangiogenic activity of prostate-specific antigen. J. Natl. Cancer Inst.91, 1635–1640.10.1093/jnci/91.19.1635Search in Google Scholar

Fortier, A.H., Holaday, J.W., Liang, H., Dey, C., Grella, D.K., Holland-Linn, J., Vu, H., Plum, S.M., and Nelson, B.J. (2003). Recombinant prostate specific antigen inhibits angiogenesis in vitro and in vivo. Prostate56, 212–219.10.1002/pros.10256Search in Google Scholar

Graveley, B.R. (2001). Alternative splicing: increasing diversity in the proteomic world. Trends Genet.17, 100–107.10.1016/S0168-9525(00)02176-4Search in Google Scholar

Herrala, A., Kurkela, R., Porvari, K., Isomaki, R., Henttu, P., and Vihko, P. (1997). Human prostate-specific glandular kallikrein is expressed as an active and an inactive protein. Clin. Chem.43, 279–284.10.1093/clinchem/43.2.279Search in Google Scholar

Heuze, N., Olayat, S., Gutman, N., Zani, M.L., and Courty, Y. (1999). Molecular cloning and expression of an alternative hKLK3 transcript coding for a variant protein of prostate-specific antigen. Cancer Res.59, 2820–2824.Search in Google Scholar

Heuze-Vourc'h, N., Leblond, V., Olayat, S., Gauthier, F., and Courty, Y. (2001). Characterization of PSA-RP2, a protein related to prostate-specific antigen and encoded by alternative hKLK3 transcripts. Eur. J. Biochem.268, 4408–4413.10.1046/j.1432-1327.2001.02367.xSearch in Google Scholar PubMed

Heuze-Vourc'h, N., Leblond, V., and Courty, Y. (2003). Complex alternative splicing of the hKLK3 gene coding for the tumor marker PSA (prostate-specific antigen). Eur. J. Biochem.270, 706–714.10.1046/j.1432-1033.2003.03425.xSearch in Google Scholar PubMed

Hilz, H., Noldus, J., Hammerer, P., Buck, F., Luck, M., and Huland, H. (1999). Molecular heterogeneity of free PSA in sera of patients with benign and malignant prostate tumors. Eur. Urol.36, 286–292.10.1159/000020006Search in Google Scholar PubMed

Hooper, J.D., Bui, L.T., Rae, F.K., Harvey, T.J., Myers, S.A., Ashworth, L.K., and Clements, J.A. (2001). Identification and characterization of KLK14, a novel kallikrein serine protease gene located on human chromosome 19q13.4 and expressed in prostate and skeletal muscle. Genomics73, 117–122.Search in Google Scholar

Johnson, J.M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P.M., Armour, C.D., Santos, R., Schadt, E.E., Stoughton, R., and Shoemaker, D.D. (2003). Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science302, 2141–2144.10.1126/science.1090100Search in Google Scholar PubMed

Komatsu, N., Takata, M., Otsuki, N., Toyama, T., Ohka, R., Takehara, K., and Saijoh, K. (2003). Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages. J. Invest. Dermatol.121, 542–549.10.1046/j.1523-1747.2003.12363.xSearch in Google Scholar PubMed

Korkmaz, K.S., Korkmaz, C.G., Pretlow, T.G., and Saatcioglu, F. (2001). Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and regulation by multiple hormones. DNA Cell Biol.20, 435–445.10.1089/104454901750361497Search in Google Scholar

Kornblihtt, A.R., de la Mata, M., Fededa, J.P., Munoz, M.J., and Nogues, G. (2004). Multiple links between transcription and splicing. RNA10, 1489–1498.10.1261/rna.7100104Search in Google Scholar

Kozak, M. (1999). Initiation of translation in prokaryotes and eukaryotes. Gene234, 187–208.10.1016/S0378-1119(99)00210-3Search in Google Scholar

Krawczak, M., Reiss, J., and Cooper, D.N. (1992). The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet.90, 41–54.10.1007/BF00210743Search in Google Scholar

Kumar, A., Mikolajczyk, S.D., Hill, T.M., Millar, L.S., and Saedi, M.S. (2000). Different proportions of various prostate-specific antigen (PSA) and human kallikrein 2 (hK2) forms are present in noninduced and androgen-induced LNCaP cells. Prostate44, 248–254.10.1002/1097-0045(20000801)44:3<248::AID-PROS10>3.0.CO;2-DSearch in Google Scholar

Kurkela, R., Herrala, A., Henttu, P., Nai, H., and Vihko, P. (1995). Expression of active, secreted human prostate-specific antigen by recombinant baculovirus-infected insect cells on a pilot-scale. Biotechnology13, 1230–1234.10.1038/nbt1195-1230Search in Google Scholar

Kurlender, L., Yousef, G.M., Memari, N., Robb, J.D., Michael, I.P., Borgono, C., Katsaros, D., Stephan, C., Jung, K., and Diamandis, E.P. (2004). Differential expression of a human kallikrein 5 (KLK5) splice variant in ovarian and prostate cancer. Tumour Biol.25, 149–156.10.1159/000079147Search in Google Scholar

Kurlender, L., Borgono, C., Michael, I.P., Obiezu, C., Elliott, M.B., Yousef, G.M., and Diamandis, E.P. (2005). A survey of alternative transcripts of human tissue kallikrein genes. Biochim. Biophys. Acta1755, 1–14.10.1016/j.bbcan.2005.02.001Search in Google Scholar

Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., et al. (2001). Initial sequencing and analysis of the human genome. Nature409, 860–921.Search in Google Scholar

Landry, J.R., Mager, D.L., and Wilhelm, B.T. (2003). Complex controls: the role of alternative promoters in mammalian genomes. Trends Genet.19, 640–648.10.1016/j.tig.2003.09.014Search in Google Scholar

Liu, X.F., Essand, M., Vasmatzis, G., Lee, B., and Pastan, I. (1999). Identification of three new alternate human kallikrein 2 transcripts: evidence of long transcript and alternative splicing. Biochem. Biophys. Res. Commun.264, 833–839.10.1006/bbrc.1999.1595Search in Google Scholar

Magklara, A., Scorilas, A., Katsaros, D., Massobrio, M., Yousef, G.M., Fracchioli, S., Danese, S., and Diamandis, E.P. (2001). The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer. Clin. Cancer Res.7, 806–811.Search in Google Scholar

Matallanas, D., Arozarena, I., Berciano, M.T., Aaronson, D.S., Pellicer, A., Lafarga, M., and Crespo, P. (2003). Differences in the inhibitory specificities of H-Ras, K-Ras, and N-Ras (N17) dominant negative mutants are related to their membrane microlocalization. J. Biol. Chem.278, 4572–4581.10.1074/jbc.M209807200Search in Google Scholar

Meng, F.J., Shan, A., Jin, L., and Young, C.Y. (2002). The expression of a variant prostate-specific antigen in human prostate. Cancer Epidemiol. Biomarkers Prev.11, 305–309.Search in Google Scholar

Mercatante, D. and Kole, R. (2000). Modification of alternative splicing pathways as a potential approach to chemotherapy. Pharmacol. Ther.85, 237–243.10.1016/S0163-7258(99)00067-4Search in Google Scholar

Michael, I.P., Kurlender, L., Memari, N., Yousef, G.M., Du, D., Grass, L., Stephan, C., Jung, K., and Diamandis, E.P. (2005). Intron retention: a common splicing event within the human kallikrein gene family. Clin. Chem.51, 506–515.10.1373/clinchem.2004.042341Search in Google Scholar

Mignone, F., Gissi, C., Liuni, S., and Pesole, G. (2002). Untranslated regions of mRNAs. Genome Biol.3, reviews/0004.10.1186/gb-2002-3-3-reviews0004Search in Google Scholar

Mikolajczyk, S.D., Millar, L.S., Marker, K.M., Wang, T.J., Rittenhouse, H.G., Marks, L.S., and Slawin, K.M. (2000). Seminal plasma contains BPSA, a molecular form of prostate-specific antigen that is associated with benign prostatic hyperplasia. Prostate45, 271–276.10.1002/1097-0045(20001101)45:3<271::AID-PROS11>3.0.CO;2-TSearch in Google Scholar

Mitsui, S., Tsuruoka, N., Yamashiro, K., Nakazato, H., and Yamaguchi, N. (1999). A novel form of human neuropsin, a brain-related serine protease, is generated by alternative splicing and is expressed preferentially in human adult brain. Eur. J. Biochem.260, 627–634.10.1046/j.1432-1327.1999.00213.xSearch in Google Scholar

Mitsui, S., Okui, A., Kominami, K., Uemura, H., and Yamaguchi, N. (2000a). cDNA cloning and tissue-specific splicing variants of mouse hippostasin/TLSP (PRSS20). Biochim. Biophys. Acta1494, 206–210.10.1016/S0167-4781(00)00206-2Search in Google Scholar

Mitsui, S., Yamada, T., Okui, A., Kominami, K., Uemura, H., and Yamaguchi, N. (2000b). A novel isoform of a kallikrein-like protease, TLSP/hippostasin, (PRSS20), is expressed in the human brain and prostate. Biochem. Biophys. Res. Commun.272, 205–211.10.1006/bbrc.2000.2761Search in Google Scholar

Modrek, B. and Lee, C. (2002). A genomic view of alternative splicing. Nat. Genet.30, 13–19.10.1038/ng0102-13Search in Google Scholar

Nakamura, T., Mitsui, S., Okui, A., Kominami, K., Nomoto, T., Ukimura, O., Kawauchi, A., Miki, T., and Yamaguchi, N. (2001). Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines. Prostate49, 72–78.10.1002/pros.1119Search in Google Scholar

Nakamura, T., Mitsui, S., Okui, A., Miki, T., and Yamaguchi, N. (2003a). Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate. Prostate54, 299–305.10.1002/pros.10191Search in Google Scholar

Nakamura, T., Stephan, C., Scorilas, A., Yousef, G.M., Jung, K., and Diamandis, E.P. (2003b). Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues. Urology61, 1042–1046.10.1016/S0090-4295(02)02443-3Search in Google Scholar

Nam, R.K., Zhang, W.W., Trachtenberg, J., Diamandis, E., Toi, A., Emami, M., Ho, M., Sweet, J., Evans, A., Jewett, M.A., and Narod, S.A. (2003). Single nucleotide polymorphism of the human kallikrein-2 gene highly correlates with serum human kallikrein-2 levels and in combination enhances prostate cancer detection. J. Clin. Oncol.21, 2312–2319.10.1200/JCO.2003.11.007Search in Google Scholar

Obiezu, C.V. and Diamandis, E.P. (2005). Human tissue kallikrein gene family: applications in cancer. Cancer Lett.224, 1–22.10.1016/j.canlet.2004.09.024Search in Google Scholar

Pampalakis, G., Kurlender, L., Diamandis, E.P., and Sotiropoulou, G. (2004). Cloning and characterization of novel isoforms of the human kallikrein 6 gene. Biochem. Biophys. Res. Commun.320, 54–61.10.1016/j.bbrc.2004.04.205Search in Google Scholar

Pesole, G., Mignone, F., Gissi, C., Grillo, G., Licciulli, F., and Liuni, S. (2001). Structural and functional features of eukaryotic mRNA untranslated regions. Gene276, 73–81.10.1016/S0378-1119(01)00674-6Search in Google Scholar

Peter, J., Unverzagt, C., Krogh, T.N., Vorm, O., and Hoesel, W. (2001). Identification of precursor forms of free prostate-specific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry. Cancer Res.61, 957–962.Search in Google Scholar

Pozniak, C.D., Radinovic, S., Yang, A., McKeon, F., Kaplan, D.R., and Miller, F.D. (2000). An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science289, 304–306.10.1126/science.289.5477.304Search in Google Scholar

Rae, F., Bulmer, B., Nicol, D., and Clements, J. (1999). The human tissue kallikreins (KLKs 1–3) and a novel KLK1 mRNA transcript are expressed in a renal cell carcinoma cDNA library. Immunopharmacology45, 83–88.10.1016/S0162-3109(99)00059-4Search in Google Scholar

Riegman, P.H., Vlietstra, R.J., van der Korput, J.A., Romijn, J.C., and Trapman, J. (1989). Characterization of the prostate-specific antigen gene: a novel human kallikrein-like gene. Biochem. Biophys. Res. Commun.159, 95–102.10.1016/0006-291X(89)92409-1Search in Google Scholar

Ross, P., Hall, L., Smirnov, I., and Haff, L. (1998). High level multiplex genotyping by MALDI-TOF mass spectrometry. Nat. Biotechnol.16, 1347–1351.10.1038/4328Search in Google Scholar PubMed

Shinmura, K., Tao, H., Yamada, H., Kataoka, H., Sanjar, R., Wang, J., Yoshimura, K., and Sugimura, H. (2004). Splice-site genetic polymorphism of the human kallikrein 12 (KLK12) gene correlates with no substantial expression of KLK12 protein having serine protease activity. Hum. Mutat.24, 273–274.10.1002/humu.9270Search in Google Scholar

Slawin, K.M., Shariat, S.F., Nguyen, C., Leventis, A.K., Song, W., Kattan, M.W., Young, C.Y., Tindall, D.J., and Wheeler, T.M. (2000). Detection of metastatic prostate cancer using a splice variant-specific reverse transcriptase-polymerase chain reaction assay for human glandular kallikrein. Cancer Res.60, 7142–7148.Search in Google Scholar

Slim, R., Torremocha, F., Moreau, T., Pizard, A., Hunt, S.C., Vuagnat, A., Williams, G.H., Gauthier, F., Jeunemaitre, X., and Alhenc-Gelas, F. (2002). Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. J. Am. Soc. Nephrol.13, 968–976.10.1681/ASN.V134968Search in Google Scholar

Sonenberg, N. (1994). mRNA translation: influence of the 5′ and 3′ untranslated regions. Curr. Opin. Genet. Dev.4, 310–315.10.1016/S0959-437X(05)80059-0Search in Google Scholar

Sun, X.Y., Donald, S.P., and Phang, J.M. (2001). Testosterone and prostate specific antigen stimulate generation of reactive oxygen species in prostate cancer cells. Carcinogenesis22, 1775–1780.10.1093/carcin/22.11.1775Search in Google Scholar

Tanaka, T., Isono, T., Yoshiki, T., Yuasa, T., and Okada, Y. (2000). A novel form of prostate-specific antigen transcript produced by alternative splicing. Cancer Res.60, 56–59.Search in Google Scholar

Underwood, L.J., Tanimoto, H., Wang, Y., Shigemasa, K., Parmley, T.H., and O'Brien, T.J. (1999). Cloning of tumor-associated differentially expressed gene-14, a novel serine protease overexpressed by ovarian carcinoma. Cancer Res.59, 4435–4439.Search in Google Scholar

van der Velden, A.W. and Thomas, A.A. (1999). The role of the 5′ untranslated region of an mRNA in translation regulation during development. Int. J. Biochem. Cell. Biol.31, 87–106.10.1016/S1357-2725(98)00134-4Search in Google Scholar

Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., Sutton, G.G., Smith, H.O., Yandell, M., Evans, C.A., Holt, R.A., et al. (2001). The sequence of the human genome. Science291, 1304–1351.10.1126/science.1058040Search in Google Scholar PubMed

Xi, Z., Klokk, T.I., Korkmaz, K., Kurys, P., Elbi, C., Risberg, B., Danielsen, H., Loda, M., and Saatcioglu, F. (2004). Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. Cancer Res.64, 2365–2370.10.1158/0008-5472.CAN-03-2025Search in Google Scholar PubMed

Xu, Q. and Lee, C. (2003). Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences. Nucleic Acids Res.31, 5635–5643.10.1093/nar/gkg786Search in Google Scholar PubMed PubMed Central

Xu, Q., Modrek, B., and Lee, C. (2002). Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res.30, 3754–3766.10.1093/nar/gkf492Search in Google Scholar PubMed PubMed Central

Yeo, G.W., Van Nostrand, E., Holste, D., Poggio, T., and Burge, C.B. (2005). Identification and analysis of alternative splicing events conserved in human and mouse. Proc. Natl. Acad. Sci. USA102, 2850–2855.10.1073/pnas.0409742102Search in Google Scholar PubMed PubMed Central

Yousef, G.M. and Diamandis, E.P. (2001). The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr. Rev.22, 184–204.Search in Google Scholar

Yousef, G.M., White, N.M., Kurlender, L., Michael, I., Memari, N., Robb, J.D., Katsaros, D., Stephan, C., Jung, K., and Diamandis, E.P. (2004). The kallikrein gene 5 splice variant 2 is a new biomarker for breast and ovarian cancer. Tumour Biol.25, 221–227.10.1159/000081384Search in Google Scholar PubMed

Yousef, G.M., White, N.M., Michael, I.P., Cho, J.C., Robb, J.D., Kurlender, L., Khan, S., and Diamandis, E.P. (2005). Identification of new splice variants and differential expression of the human kallikrein 10 gene, a candidate cancer biomarker. Tumour Biol.26, 227–235.10.1159/000087377Search in Google Scholar PubMed

Zaika, A.I., Slade, N., Erster, S.H., Sansome, C., Joseph, T.W., Pearl, M., Chalas, E., and Moll, U.M. (2002). DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. J. Exp. Med.196, 765–780.10.1084/jem.20020179Search in Google Scholar PubMed PubMed Central

Zhao, J., Hyman, L., and Moore, C. (1999). Formation of mRNA 3′ ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis. Microbiol. Mol. Biol. Rev.63, 405–445.10.1128/MMBR.63.2.405-445.1999Search in Google Scholar PubMed PubMed Central

Published Online: 2006-06-26
Published in Print: 2006-06-01

©2006 by Walter de Gruyter Berlin New York

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