Distinct roles of first exon variants of the tumor-suppressor Patched1 in Hedgehog signaling

Oncogene

Volumn 26, Issue 34, 2007, Pages 4889-4896

  Shimokawa, T ^a   Svard J ^a   Heby Henricson, K ^a   Teglund, S ^a   Toftgard R ^a   Zaphiropoulos, P G ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Alternative splicing; GLI; Post transcriptional regulation

Indexed keywords

ISOPROTEIN; PROTEIN; PROTEIN PATCHED 1; PROTEIN SMOOTHENED; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GLIOMA 1; TRANSCRIPTION FACTOR GLIOMA 2; UNCLASSIFIED DRUG;

ALTERNATIVE RNA SPLICING; AMINO TERMINAL SEQUENCE; ANIMAL TISSUE; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; EMBRYO; EMBRYO DEVELOPMENT; EXON; GENETIC VARIABILITY; IN SITU HYBRIDIZATION; MOLECULAR BIOLOGY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN STRUCTURE; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; STEADY STATE; TUMOR SUPPRESSOR GENE;

ALTERNATIVE SPLICING; ANIMALS; BASE SEQUENCE; EMBRYONIC DEVELOPMENT; EXONS; HEDGEHOG PROTEINS; HUMANS; MICE; MOLECULAR SEQUENCE DATA; ONCOGENE PROTEINS; PROTEIN ISOFORMS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; TRANS-ACTIVATORS; TUMOR SUPPRESSOR PROTEINS;

ERINACEIDAE;

EID: 34547478739     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/sj.onc.1210301     Document Type: Article

References (31)

1. Ågren M, Kogerman P, Kleman MI, Wessling M, Toftgård R. (2004). Expression of the PTCH1 tumor suppressor gene is regulated by alternative promoters and a single functional Gli-binding site. Gene 330: 101-114.
2. Bai CB, Auerbach W, Lee JS, Stephen D, Joyner AL. (2002). Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development 129: 4753-4761.
3. Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J et al. (2006). Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38: 626-635.
4. Carpenter D, Stone DM, Brush J, Ryan A, Armanini M, Frantz G et al. (1998). Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci USA 95: 13630-13634.
5. Eichberger T, Sander V, Schnidar H, Regl G, Kasper M, Schmid C et al. (2006). Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes. Genomics 87: 616-632.
6. Goodrich LV, Milenkovic L, Higgins KM, Scott MP. (1997). Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277: 1109-1113.
7. Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B et al. (1996a). A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities. J Biol Chem 271: 12125-12128.
8. Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A et al. (1996b). Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85: 841-851.
9. Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G, Zimmer A. (1998). Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat Med 4: 619-622.
10. Hughes TA. (2006). Regulation of gene expression by alternative untranslated regions. Trends Genet 22: 119-122.
11. Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM et al. (1996). Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272: 1668-1671.
12. Kalderon D. (2005). The mechanism of hedgehog signal transduction. Biochem Soc Trans 33: 1509-1512.
13. Kampa D, Cheng J, Kapranov P, Yamanaka M, Brubaker S, Cawley S et al. (2004). Novel RNAs identified from an indepth analysis of the transcriptome of human chromosomes 21 and 22. Genome Res 14: 331-342.
14. Kogerman P, Krause D, Rahnama F, Kogerman L, Unden AB, Zaphiropoulos PG et al. (2002). Alternative first exons of PTCH1 are differentially regulated in vivo and may confer different functions to the PTCH1 protein. Oncogene 21: 6007-6016.
15. Lee Y, Miller HL, Russell HR, Boyd K, Curran T, McKinnon PJ. (2006). Patched2 modulates tumorigenesis in patched1 heterozygous mice. Cancer Res 66: 6964-6971.
16. Liu W, Li G, Chien JS, Raft S, Zhang H, Chiang C et al. (2002). Sonic hedgehog regulates otic capsule chondro-genesis and inner ear development in the mouse embryo. Dev Biol 248: 240-250.
17. Motoyama J, Takabatake T, Takeshima K, Hui C. (1998). Ptch2, a second mouse Patched gene is co-expressed with Sonic hedgehog. Nat Genet 18: 104-106.
18. Nagao K, Toyoda M, Takeuchi-Inoue K, Fujii K, Yamada M, Miyashita T. (2005). Identification and characterization of multiple isoforms of a murine and human tumor suppressor, patched, having distinct first exons. Genomics 85: 462-471.
19. Nybakken K, Vokes SA, Lin TY, McMahon AP, Perrimon N. (2005). A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway. Nat Genet 37: 1323-1332.
20. Rahnama F, Shimokawa T, Lauth M, Finta C, Kogerman P, Teglund S et al. (2006). Inhibition of GLI1 gene activation by Patched1. Biochem J 394: 19-26.
21. Rahnama F, Toftgård R, Zaphiropoulos PG. (2004). Distinct roles of PTCH2 splice variants in Hedgehog signalling. Biochem J 378: 325-334.
22. Roessler E, Ermilov AN, Grange DK, Wang A, Grachtchouk M, Dlugosz AA et al. (2005). A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2. Hum Mol Genet 14: 2181-2188.
23. Sanchez P, Hernandez AM, Stecca B, Kahler AJ, DeGueme AM, Barrett A et al. (2004). Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA 101: 12561-12566.
24. Shimokawa T, Rahnama F, Zaphiropoulos PG. (2004). A novel first exon of the Patched1 gene is upregulated by Hedgehog signaling resulting in a protein with pathway inhibitory functions. FEBS Lett 578: 157-162.
25. Smyth I, Narang MA, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G et al. (1999). Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol Genet 8: 291-297.
26. Smyth I, Wicking C, Wainwright B, Chenevix-Trench G. (1998). The effects of splice site mutations in patients with naevoid basal cell carcinoma syndrome. Hum Genet 102: 598-601.
27. Speek M, Njunkova O, Pata I, Valdre E, Kogerman P. (2006). A potential role of alternative splicing in the regulation of the transcriptional activity of human GLI2 in gonadal tissues. BMC Mol Biol 7: 13.
28. Svärd J, Heby-Henricson K, Persson-Lek M, Rozell B, Lauth M, Bergström Å et al. (2006). Genetic elimination of suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev Cell 10: 187-197.
29. Uchikawa H, Toyoda M, Nagao K, Miyauchi H, Nishikawa R, Fujii K et al. (2006). Brain- and heart-specific Patched-1 containing exon 12b is a dominant negative isoform and is expressed in medulloblastomas. Biochem Biophys Res Commun 349: 277-283.
30. Wang XQ, Rothnagel JA. (2001). Post-transcriptional regulation of the GLI1 oncogene by the expression of alternative 5′ untranslated regions. J Biol Chem 276: 1311-1316.
31. Zaphiropoulos PG, Unden AB, Rahnama F, Hollingsworth RE, Toftgård R. (1999). PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas. Cancer Res 59: 787-792.