The translation of an antiapoptotic protein HIAP2 is regulated by an upstream open reading frame

Warnakulasuriyarachchi, Dinesh; Ungureanu, Nicoleta Hosszu; Holčı́k, Martin

doi:10.1038/sj.cdd.4401256

Cited by 27 publications

(37 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings highlight the limitations of such assumptions. Although non-AUG-initiated uORFs have been reported before (38), there has not yet been a systematic attempt to investigate how widespread they might be.…”

Section: Discussionmentioning

confidence: 99%

uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs

Ivanov

Loughran

Atkins

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In a minority of eukaryotic mRNAs, a small functional upstream ORF (uORF), often performing a regulatory role, precedes the translation start site for the main product(s). Here, conserved uORFs in numerous ornithine decarboxylase homologs are identified from yeast to mammals. Most have noncanonical evolutionarily conserved start codons, the main one being AUU, which has not been known as an initiator for eukaryotic chromosomal genes. The AUG-less uORF present in mouse antizyme inhibitor, one of the ornithine decarboxylase homologs in mammals, mediates polyamine-induced repression of the downstream main ORF. This repression is part of an autoregulatory circuit, and one of its sensors is the AUU codon, which suggests that translation initiation codon identity is likely used for regulation in eukaryotes.antizyme ͉ AUU ͉ non-AUG ͉ polyamines ͉ upstream ORF

show abstract

Section: Discussionmentioning

confidence: 99%

uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs

Ivanov

Loughran

Atkins

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…24 Translation regulation by upstream ORFs (uORF) occurs in a number of genes, such as Fli-1, where it is mediated by two short uORFs, one using a GUG start codon, 25 and HIAP2, whose translation is controlled by a uORF with a CUG start codon. 26 One can thus speculate that a disruption in HK1 translation regulation, caused by the tyrosine for a Stop substitution in a uORF with a non-AUG start codon, could be the mutational mechanism in HMSNR.…”

Section: Discussionmentioning

confidence: 99%

A mutation in an alternative untranslated exon of hexokinase 1 associated with Hereditary Motor and Sensory Neuropathy – Russe (HMSNR)

et al. 2009

View full text Add to dashboard Cite

Hereditary Motor and Sensory Neuropathy -Russe (HMSNR) is a severe autosomal recessive disorder, identified in the Gypsy population. Our previous studies mapped the gene to 10q22-q23 and refined the gene region to B70 kb. Here we report the comprehensive sequencing analysis and fine mapping of this region, reducing it to B26 kb of fully characterised sequence spanning the upstream exons of Hexokinase 1 (HK1). We identified two sequence variants in complete linkage disequilibrium, a G4C in a novel alternative untranslated exon (AltT2) and a G4A in the adjacent intron, segregating with the disease in affected families and present in the heterozygote state in only 5/790 population controls. Sequence conservation of the AltT2 exon in 16 species with invariable preservation of the G allele at the mutated site, strongly favour the exonic change as the pathogenic mutation. Analysis of the Hk1 upstream region in mouse mRNA from testis and neural tissues showed an abundance of AltT2-containing transcripts generated by extensive, developmentally regulated alternative splicing. Expression is very low compared with ubiquitous Hk1 and all transcripts skip exon1, which encodes the protein domain responsible for binding to the outer mitochondrial membrane, and regulation of energy production and apoptosis. Hexokinase activity measurement and immunohistochemistry of the peripheral nerve showed no difference between patients and controls. The mutational mechanism and functional effects remain unknown and could involve disrupted translational regulation leading to increased anti-apoptotic activity (suggested by the profuse regenerative activity in affected nerves), or impairment of an unknown HK1 function in the peripheral nervous system (PNS).

show abstract

“…Some of these cellular IRESes are utilized during different stress conditions such as hypoxia or heat shock. [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] In light of the above, a major question that became of interest to the cell death community, and will be addressed in detail in this issue of CDD, is whether translational switches are part of the PCD process, and more specifically, whether a shift from cap-dependent to IRES-mediated translation occurs under certain settings of cell death. In fact, it turned out that induction of type I PCD, for example, is associated with a rapid and substantial shut-off of overall protein synthesis in the cell.…”

Section: Switching the Initiation Of Protein Synthesis From Cap-depenmentioning

confidence: 99%

DAP5 and IRES-mediated translation during programmed cell death

Marash

Kimchi

2005

Cell Death Differ

View full text Add to dashboard Cite

DAP5 (Death Associated Protein 5), also named p97 and NAT1, is a member of the eIF4G family that lacks the eIF4E binding site. Its function was linked to programmed cell death (PCD) based on the seminal finding that a fragment of DAP5/ p97 protein, which acted in a dominant-negative manner, protected against IFN-gamma (IFN-g)-induced cell death. Subsequently, it was found that DAP5 protein is activated during cell death by caspase cleavage, yielding a C-terminaltruncated protein of 86 kDa. The p86 form promotes internal ribosome entry site (IRES)-dependent translation of several mRNAs including Apaf-1, c-myc, XIAP, HIAP2 and DAP5 itself, which carries an IRES element in its 5 0 UTR. The activation of DAP5 IRES creates a positive feedback loop, which results in sustained translation of DAP5 protein during PCD under conditions of reduced cap-dependent translation. DAP5 deficiency prevents embryonic stem (ES) cell differentiation, suggesting a wider range of DAP5 mRNA targets and additional mechanisms that might activate the protein.

show abstract

The translation of an antiapoptotic protein HIAP2 is regulated by an upstream open reading frame

Cited by 27 publications

References 18 publications

uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs

uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs

A mutation in an alternative untranslated exon of hexokinase 1 associated with Hereditary Motor and Sensory Neuropathy – Russe (HMSNR)

DAP5 and IRES-mediated translation during programmed cell death

Contact Info

Product

Resources

About