* 147572

INTERFERON-ALPHA-INDUCIBLE PROTEIN 6; IFI6


Alternative titles; symbols

INTERFERON-INDUCED PROTEIN IFI-6-16; IFI616
G1P3


HGNC Approved Gene Symbol: IFI6

Cytogenetic location: 1p35.3     Genomic coordinates (GRCh38): 1:27,666,064-27,672,192 (from NCBI)


TEXT

Cloning and Expression

By differential screening of an alpha-interferon (IFNA; 147660)-induced neuroblastoma cell cDNA library, followed by screening an IFNA-treated Daudi lymphoblastoid cell cDNA library, Kelly et al. (1986) cloned IFI6, which they called 6-16. The deduced 130-amino acid protein is hydrophobic and contains an N-terminal signal peptide.


Gene Function

Kelly et al. (1986) showed that IFI6 was induced in HeLa cells by IFNA and IFNB (147640). Following transfection in mouse cells, human IFI6 was expressed in response to mouse Ifna and Ifnb, but not Ifng (147570), with the same kinetics and dose response as in human cells.

Itzhaki and Porter (1991) reported a method for targeted disruption of the IFI6 gene and detection by secretion of human growth hormone (GH1; 139250).

Cheriyath et al. (2007) showed that treatment of human myeloma cells with IFN-alpha-2b (see IFNA2; 147562) for 24 hours antagonized TRAIL (TNFSF10; 603598)-mediated apoptosis, but after 72 hours it augmented TRAIL apoptotic activity. The antiapoptotic activity of IFN-alpha-2b was associated with increased expression of G1P3. Ectopically expressed G1P3 localized to mitochondria and antagonized TRAIL-mediated mitochondrial potential loss, cytochrome c release, and apoptosis. Conversely, RNA interference-mediated downregulation of G1P3 restored IFN-alpha-2b-induced apoptosis. Cheriyath et al. (2007) concluded that curtailing G1P3-mediated antiapoptotic signals may improve therapies for myeloma and other malignancies.


Gene Structure

Kelly et al. (1986) determined that the IFI6 gene contains 5 exons and has a TATA box upstream of the transcription initiation site.

Porter et al. (1988) described the interferon response element of the human IFI6 gene.


Mapping

By somatic cell hybrid analysis, Clauss et al. (1990) mapped the IFI6 gene to chromosome 1.

Itzhaki et al. (1992) reported that the IFI6 gene maps to chromosome 1p35, based on the work of others using fluorescence in situ hybridization. Itzhaki et al. (1992) used telomere-associated chromosome fragmentation (TACF), a novel approach for chromosome mapping based on the nontargeted introduction of clone telomeres into mammalian chromosomes, to target telomeric DNA to the IFI6 gene on chromosome 1p. They deduced that the IFI6 gene is oriented away from the centromere by targeting telomeric DNA to the specific locus by homologous recombination, using a selection strategy that imposed the requirement that the telomeric DNA be oriented in the same direction as the IFI6 gene.


REFERENCES

  1. Cheriyath, V., Glaser, K. B., Waring, J. F., Baz, R., Hussein, M. A., Borden, E. C. G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells. J. Clin. Invest. 117: 3107-3117, 2007. [PubMed: 17823654, images, related citations] [Full Text]

  2. Clauss, I. M., Wathelet, M. G., Szpirer, J., Content, J., Islam, M. Q., Levan, G., Szpirer, C., Huez, G. A. Chromosomal localization of two human genes inducible by interferons, double-stranded RNA, and viruses. Cytogenet. Cell Genet. 53: 166-168, 1990. [PubMed: 1695131, related citations] [Full Text]

  3. Itzhaki, J. E., Barnett, M. A., MacCarthy, A. B., Buckle, V. J., Brown, W. R. A., Porter, A. C. G. Targeted breakage of a human chromosome mediated by cloned human telomeric DNA. Nature Genet. 2: 283-287, 1992. [PubMed: 1303280, related citations] [Full Text]

  4. Itzhaki, J. E., Porter, A. C. G. Targeted disruption of a human interferon-inducible gene detected by secretion of human growth hormone. Nucleic Acids Res. 19: 3835-3842, 1991. [PubMed: 1713665, related citations] [Full Text]

  5. Kelly, J. M., Porter, A. C. G., Chernajovsky, Y., Gilbert, C. S., Stark, G. R., Kerr, I. M. Characterization of a human gene inducible by alpha- and beta-interferons and its expression in mouse cells. EMBO J. 5: 1601-1606, 1986. [PubMed: 3017706, related citations] [Full Text]

  6. Porter, A. C. G., Chernajovsky, Y., Dale, T. C., Gilbert, C. S., Stark, G. R., Kerr, I. M. Interferon response element of the human gene 6-16. EMBO J. 7: 85-92, 1988. [PubMed: 3359997, related citations] [Full Text]


Matthew B. Gross - updated : 11/06/2007
Patricia A. Hartz - updated : 11/2/2007
Creation Date:
Victor A. McKusick : 10/5/1990
mgross : 11/06/2007
terry : 11/2/2007
mgross : 8/14/2007
mgross : 8/14/2007
carol : 5/24/1999
carol : 8/20/1998
carol : 6/30/1998
jason : 6/17/1994
carol : 3/1/1993
carol : 2/25/1993
carol : 2/4/1993
carol : 1/26/1993
supermim : 3/16/1992

* 147572

INTERFERON-ALPHA-INDUCIBLE PROTEIN 6; IFI6


Alternative titles; symbols

INTERFERON-INDUCED PROTEIN IFI-6-16; IFI616
G1P3


HGNC Approved Gene Symbol: IFI6

Cytogenetic location: 1p35.3     Genomic coordinates (GRCh38): 1:27,666,064-27,672,192 (from NCBI)


TEXT

Cloning and Expression

By differential screening of an alpha-interferon (IFNA; 147660)-induced neuroblastoma cell cDNA library, followed by screening an IFNA-treated Daudi lymphoblastoid cell cDNA library, Kelly et al. (1986) cloned IFI6, which they called 6-16. The deduced 130-amino acid protein is hydrophobic and contains an N-terminal signal peptide.


Gene Function

Kelly et al. (1986) showed that IFI6 was induced in HeLa cells by IFNA and IFNB (147640). Following transfection in mouse cells, human IFI6 was expressed in response to mouse Ifna and Ifnb, but not Ifng (147570), with the same kinetics and dose response as in human cells.

Itzhaki and Porter (1991) reported a method for targeted disruption of the IFI6 gene and detection by secretion of human growth hormone (GH1; 139250).

Cheriyath et al. (2007) showed that treatment of human myeloma cells with IFN-alpha-2b (see IFNA2; 147562) for 24 hours antagonized TRAIL (TNFSF10; 603598)-mediated apoptosis, but after 72 hours it augmented TRAIL apoptotic activity. The antiapoptotic activity of IFN-alpha-2b was associated with increased expression of G1P3. Ectopically expressed G1P3 localized to mitochondria and antagonized TRAIL-mediated mitochondrial potential loss, cytochrome c release, and apoptosis. Conversely, RNA interference-mediated downregulation of G1P3 restored IFN-alpha-2b-induced apoptosis. Cheriyath et al. (2007) concluded that curtailing G1P3-mediated antiapoptotic signals may improve therapies for myeloma and other malignancies.


Gene Structure

Kelly et al. (1986) determined that the IFI6 gene contains 5 exons and has a TATA box upstream of the transcription initiation site.

Porter et al. (1988) described the interferon response element of the human IFI6 gene.


Mapping

By somatic cell hybrid analysis, Clauss et al. (1990) mapped the IFI6 gene to chromosome 1.

Itzhaki et al. (1992) reported that the IFI6 gene maps to chromosome 1p35, based on the work of others using fluorescence in situ hybridization. Itzhaki et al. (1992) used telomere-associated chromosome fragmentation (TACF), a novel approach for chromosome mapping based on the nontargeted introduction of clone telomeres into mammalian chromosomes, to target telomeric DNA to the IFI6 gene on chromosome 1p. They deduced that the IFI6 gene is oriented away from the centromere by targeting telomeric DNA to the specific locus by homologous recombination, using a selection strategy that imposed the requirement that the telomeric DNA be oriented in the same direction as the IFI6 gene.


REFERENCES

  1. Cheriyath, V., Glaser, K. B., Waring, J. F., Baz, R., Hussein, M. A., Borden, E. C. G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells. J. Clin. Invest. 117: 3107-3117, 2007. [PubMed: 17823654] [Full Text: https://doi.org/10.1172/JCI31122]

  2. Clauss, I. M., Wathelet, M. G., Szpirer, J., Content, J., Islam, M. Q., Levan, G., Szpirer, C., Huez, G. A. Chromosomal localization of two human genes inducible by interferons, double-stranded RNA, and viruses. Cytogenet. Cell Genet. 53: 166-168, 1990. [PubMed: 1695131] [Full Text: https://doi.org/10.1159/000132920]

  3. Itzhaki, J. E., Barnett, M. A., MacCarthy, A. B., Buckle, V. J., Brown, W. R. A., Porter, A. C. G. Targeted breakage of a human chromosome mediated by cloned human telomeric DNA. Nature Genet. 2: 283-287, 1992. [PubMed: 1303280] [Full Text: https://doi.org/10.1038/ng1292-283]

  4. Itzhaki, J. E., Porter, A. C. G. Targeted disruption of a human interferon-inducible gene detected by secretion of human growth hormone. Nucleic Acids Res. 19: 3835-3842, 1991. [PubMed: 1713665] [Full Text: https://doi.org/10.1093/nar/19.14.3835]

  5. Kelly, J. M., Porter, A. C. G., Chernajovsky, Y., Gilbert, C. S., Stark, G. R., Kerr, I. M. Characterization of a human gene inducible by alpha- and beta-interferons and its expression in mouse cells. EMBO J. 5: 1601-1606, 1986. [PubMed: 3017706] [Full Text: https://doi.org/10.1002/j.1460-2075.1986.tb04402.x]

  6. Porter, A. C. G., Chernajovsky, Y., Dale, T. C., Gilbert, C. S., Stark, G. R., Kerr, I. M. Interferon response element of the human gene 6-16. EMBO J. 7: 85-92, 1988. [PubMed: 3359997] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb02786.x]


Contributors:
Matthew B. Gross - updated : 11/06/2007
Patricia A. Hartz - updated : 11/2/2007

Creation Date:
Victor A. McKusick : 10/5/1990

Edit History:
mgross : 11/06/2007
terry : 11/2/2007
mgross : 8/14/2007
mgross : 8/14/2007
carol : 5/24/1999
carol : 8/20/1998
carol : 6/30/1998
jason : 6/17/1994
carol : 3/1/1993
carol : 2/25/1993
carol : 2/4/1993
carol : 1/26/1993
supermim : 3/16/1992