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INTS6 (integrator complex subunit 6)

Written2006-11Ilse Wieland
Institut für Humangenetik, Otto-von-Guericke-Universitüt, Leipziger Str. 44, 39120 Magdeburg, Germany

(Note : for Links provided by Atlas : click)

Identity

Other aliasDICE1
deleted in cancer 1
DBI-1
DDX26
INT6
LocusID (NCBI) 26512
Atlas_Id 40287
Location 13q14.3  [Link to chromosome band 13q14]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
INTS6 (13q14.3) / CEP44 (4q34.1)

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

Note
  
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.
  

Bibliography

Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.
Baillat D, Hakimi MA, Näär AM, Shilatifard A, Cooch N, Shiekhattar R
Cell. 2005 ; 123 (2) : 265-276.
PMID 16239144
 
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
 
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
 
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
 
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
 
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
 
Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer.
Röpke A, Buhtz P, Böhm M, Seger J, Wieland I, Allhoff EP, Wieacker PF
Oncogene. 2005 ; 24 (44) : 6667-6675.
PMID 16007164
 
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
 
Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas.
Wieland I, Arden KC, Michels D, Klein-Hitpass L, Böhm 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, Röpke A, Stumm M, Sell C, Weidle UH, Wieacker PF
Oncology research. 2001 ; 12 (11-12) : 491-500.
PMID 11939413
 
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
 

Citation

This paper should be referenced as such :
Wieland, I
INTS6 (integrator complex subunit 6)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):165-166.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/INTS6ID40287ch13q14.html


External links

Nomenclature
Cards
AtlasINTS6ID40287ch13q14.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)26512
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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