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A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours.

Krona C, Ejeskär K, Carén H, Abel F, Sjöberg RM, Martinsson T - Br. J. Cancer (2004)

Bottom Line: A reduced pattern of expression was also observed in a set of various tumour types.Furthermore, we determined the genomic organisation of APITD1.We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Clinical Genetics, Institute for the Health of Women and Children, Göteborg University, Sahlgrenska University Hospital-East, SE-41685 Gothenburg, Sweden.

ABSTRACT
Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

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Conserved amino acids in the translated APITD1 transcript A ORF. The first nine amino acids in the translated ORF did not align to the translated expressed sequences from other organisms in the TIGR database, and they are not shown. Percent identity with the human sequence is shown within brackets after the name of each organism. Residues which are identical or chemically similar to the human amino-acid sequence are highlighted in grey. The residues which are identical or similar among all aligned sequences are indicated under the alignment, and the TFIID-31 similar domain is framed.
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fig3: Conserved amino acids in the translated APITD1 transcript A ORF. The first nine amino acids in the translated ORF did not align to the translated expressed sequences from other organisms in the TIGR database, and they are not shown. Percent identity with the human sequence is shown within brackets after the name of each organism. Residues which are identical or chemically similar to the human amino-acid sequence are highlighted in grey. The residues which are identical or similar among all aligned sequences are indicated under the alignment, and the TFIID-31 similar domain is framed.

Mentions: The two alternative transcript versions of the APITD1 gene. Both transcripts share exons 2–5, but they differ in the starting exons and in the 3′UTR sequences. Exon 1A is located approximately 160 bp upstream of exon 1B in the genomic sequence. The translated sequence from the ORF in transcript A and the in-frame ORF in transcript B, which starts immediately prior to the putative TFIID-31 domain, is shown. The amino-acid sequence with significant similarity to the TFIID-31 domain is marked in bold face and italics. The last 622 bp of transcript A (chr1_29_927.b), which consists of exon 2 from the nearby located gene CORT and noncoding genomic sequence, is not shown.


A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours.

Krona C, Ejeskär K, Carén H, Abel F, Sjöberg RM, Martinsson T - Br. J. Cancer (2004)

Conserved amino acids in the translated APITD1 transcript A ORF. The first nine amino acids in the translated ORF did not align to the translated expressed sequences from other organisms in the TIGR database, and they are not shown. Percent identity with the human sequence is shown within brackets after the name of each organism. Residues which are identical or chemically similar to the human amino-acid sequence are highlighted in grey. The residues which are identical or similar among all aligned sequences are indicated under the alignment, and the TFIID-31 similar domain is framed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747717&req=5

fig3: Conserved amino acids in the translated APITD1 transcript A ORF. The first nine amino acids in the translated ORF did not align to the translated expressed sequences from other organisms in the TIGR database, and they are not shown. Percent identity with the human sequence is shown within brackets after the name of each organism. Residues which are identical or chemically similar to the human amino-acid sequence are highlighted in grey. The residues which are identical or similar among all aligned sequences are indicated under the alignment, and the TFIID-31 similar domain is framed.
Mentions: The two alternative transcript versions of the APITD1 gene. Both transcripts share exons 2–5, but they differ in the starting exons and in the 3′UTR sequences. Exon 1A is located approximately 160 bp upstream of exon 1B in the genomic sequence. The translated sequence from the ORF in transcript A and the in-frame ORF in transcript B, which starts immediately prior to the putative TFIID-31 domain, is shown. The amino-acid sequence with significant similarity to the TFIID-31 domain is marked in bold face and italics. The last 622 bp of transcript A (chr1_29_927.b), which consists of exon 2 from the nearby located gene CORT and noncoding genomic sequence, is not shown.

Bottom Line: A reduced pattern of expression was also observed in a set of various tumour types.Furthermore, we determined the genomic organisation of APITD1.We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Clinical Genetics, Institute for the Health of Women and Children, Göteborg University, Sahlgrenska University Hospital-East, SE-41685 Gothenburg, Sweden.

ABSTRACT
Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.

Show MeSH
Related in: MedlinePlus