| Identity |
| Other names | DICE1 |
| deleted in cancer 1 | |
| DBI-1 | |
| DDX26 | |
| INT6 | |
| Hugo | INTS6 |
| Location | 13q14.3 |
| DNA/RNA |
| Description | The DICE1 gene consists of 18 exons and contains a GpC-rich promoter. |
| Transcription | A major transcript of 4.4 kb and a minor transcript of 6.9 kb was detected in fetal and adult tissues. In adult heart, brain and skeletal muscle an additional smaller transcript of 4 kb has been detected by Northern blot analysis. The DICE1 cDNA consists of 3665 bp with a coding sequence of 2661 bp; an alternatively spliced variant generated by skipping of exon 3 has been detected specifically in brain. |
| Pseudogene | Presumably LOC285634 at 5p13.1 |
| Protein |
| Description | For the DICE1 protein 887 amino acids were predicted. A protein of approximately 100 kDaltons was detected by coupled in vitro transcription and translation. The Int6 protein was purified as an approximately 110 kDaltons polypeptide component of a nuclear Integrator complex. |
| Localisation | Mainly nuclear localisation |
| Function | Predicted motifs of DICE1 protein were a von willebrand factor a (VWFA) domain of nuclear proteins, nuclear sorting signals and a DEAD box of ATP-dependent helicases. Ectopic expression of DICE1 cDNA in tumour cells suppresses colony formation and in cell culture. The Int6 protein was purified as a subunit of a RNA polymerase II multiprotein complex with roles in transcriptional regulation and RNA processing. |
| Homology | Weak homology to members of the helicase superfamily II |
| Mutations |
| Note | Mutations in the coding sequence of DICE1/DDX26 have been infrequently detected in tumour cells. |
| Somatic | Frequent loss of heterozygosity (LOH) has been observed in lung, esophageal and prostate carcinomas. Promoter hypermethylation concomitant with reduced mRNA expression has been observed in lung and prostate carcinomas. In esophageal squamous cell carcinomas missense mutations V431I, R658Q have been detected. In prostate cancer cell line LNCaP missense mutation D546G has been described. |
| Implicated in |
| Entity | Functional inactivation of the DICE1 gene has been implicated in tumorigenesis of sporadic lung carcinomas, esophagus carcinomas, prostate carcinomas and possibly other sporadic carcinomas. |
| Abnormal Protein | A 6.3 kb fusion cDNA of a Notch-like with Dice1 cDNA (DBI-1) was detected in mouse cell line TC4. Overexpression of DBI-1 cDNA in IGF-IR transformed mouse cells compromised the mitogenic response to IGF-1 and interfered with anchorage-independent growth. |
| Oncogenesis | Downregulation of DICE1 mRNA was detected in 7 of 8 non-small cell lung carcinoma cell lines by Northern blot analysis. Microdissected non-small cell lung carcinomas showed reduced or absent expression of DICE1 mRNA by RT-PCR. Promoter hypermethylation was found in tumour cells with downregulated DICE1 expression. Aberrantly sized transcripts were detected in two non-small cell lung carcinoma cell lines. A reduced DICE1 expression was also observed in prostate cancer cell lines DU145 and LNCaP by real-time RT-PCR. DICE1 promoter hypermethylation was detected in 6 of 10 microdissected prostate cancer samples. Ectopic expression of DICE1 cDNA inhibited colony formation of human non-small cell lung carcinoma cell lines and prostate carcinoma cell lines and suppressed anchorage-independent growth of IGF-IR transformed mouse cells. |
| External links |
| Bibliography |
| DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1. |
| Hoff HB 3rd, Tresini M, Li S, Sell C |
| Experimental cell research. 1998 ; 238 (2) : 359-370. |
| PMID 9473344 |
| Analysis of the mouse MAP1B gene identifies a highly conserved 4.3 kb 3' untranslated region and provides evidence against the proposed structure of DBI-1 cDNA. |
| Meixner A, Wiche G, Propst F |
| Biochimica et biophysica acta. 1999 ; 1445 (3) : 345-350. |
| PMID 10366719 |
| Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas. |
| Wieland I, Arden KC, Michels D, Klein-Hitpass L, Bhm M, Viars CS, Weidle UH |
| Oncogene. 1999 ; 18 (32) : 4530-4537. |
| PMID 10467397 |
| Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells. |
| Wieland I, Rpke A, Stumm M, Sell C, Weidle UH, Wieacker PF |
| Oncology research. 2001 ; 12 (11-12) : 491-500. |
| PMID 11939413 |
| Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere. |
| Whittaker CA, Hynes RO |
| Molecular biology of the cell. 2002 ; 13 (10) : 3369-3387. |
| PMID 12388743 |
| Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma. |
| Li WJ, Hu N, Su H, Wang C, Goldstein AM, Wang Y, Emmert-Buck MR, Roth MJ, Guo WJ, Taylor PR |
| Oncogene. 2003 ; 22 (2) : 314-318. |
| PMID 12527901 |
| Ectopic expression of DICE1 suppresses tumor cell growth. |
| Wieland I, Sell C, Weidle UH, Wieacker P |
| Oncology reports. 2004 ; 12 (2) : 207-211. |
| PMID 15254679 |
| Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. |
| Baillat D, Hakimi MA, N§§r AM, Shilatifard A, Cooch N, Shiekhattar R |
| Cell. 2005 ; 123 (2) : 265-276. |
| PMID 16239144 |
| Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions. |
| Hern°ndez M, Papadopoulos N, Almeida TA |
| Cancer genetics and cytogenetics. 2005 ; 163 (1) : 91-92. |
| PMID 16271964 |
| Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer. |
| Rpke A, Buhtz P, Bhm M, Seger J, Wieland I, Allhoff EP, Wieacker PF |
| Oncogene. 2005 ; 24 (44) : 6667-6675. |
| PMID 16007164 |
| Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans. |
| Han SM, Lee TH, Mun JY, Kim MJ, Kritikou EA, Lee SJ, Han SS, Hengartner MO, Koo HS |
| Development (Cambridge, England). 2006 ; 133 (18) : 3597-3606. |
| PMID 16914495 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 11-2006 | Ilse Wieland |
| Citation |
| This paper should be referenced as such : |
| Wieland I . INTS6 (integrator complex subunit 6). Atlas Genet Cytogenet Oncol Haematol. November 2006 . URL : http://AtlasGeneticsOncology.org/Genes/INTS6ID40287ch13q14.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Jul 2 08:24:14 2008 |
For comments and suggestions or contributions, please contact us