Interferon-related developmental regulator 1 is a protein that in humans is encoded by the IFRD1gene.[5][6] The gene is expressed mostly in neutrophils, skeletal and cardiac muscle, the brain, and the pancreas.[5][6] The rat and the mouse homolog genes of interferon-related developmental regulator 1 gene (and their proteins) are also known with the name PC4 [7] and Tis21, respectively. IFRD1 is member of a gene family that comprises a second gene, IFRD2, also known as SKmc15.[5][6]
IFRD1 has been identified as a modifier gene for cystic fibrosis lung disease. In humans, neutrophil effector function is dependent on the type of IRFD1 polymorphism present in the individual. Human and mouse data both indicate that IFRD1 has a sizable impact on cystic fibrosis pathogenesis by regulating neutrophil effector function. [8]
Inducer of muscle regenerationedit
IFRD1(also known as PC4 or Tis7, see above) participates to the process of skeletal muscle cell differentiation. In fact, inhibition of IFRD1 function in C2C12 myoblasts, by antisense IFRD1 cDNA transfection or microinjection of anti-IFRD1 antibodies, prevents their morphological and biochemical differentiation by inhibiting the expression of MyoD and myogenin, key master genes of muscle development.[9] A role for IFRD1 in muscle differentiation has been observed also in vivo. Muscles from mice lacking IFRD1 display decreased protein and mRNA levels of MyoD, and myogenin, and after muscle crash damage in young mice there was a delay in regeneration.[10]
Recently it has been shown that upregulation of IFRD1 in vivo in injured muscle potentiates muscle regeneration by increasing the production of staminal muscle cells (satellite cells).[11] The underlying molecular mechanism lies in the ability of IFRD1 to cooperate with MyoD at inducing the transcriptional activity of MEF2C. This relies on the ability of IFRD1 to bind selectively MEF2C, thus inhibiting its interaction with HDAC4.[11][12] Therefore, IFRD1 appears to act as a positive cofactor of MyoD.[11][12] More recently it has been shown that IFRD1 potentiates muscle regeneration by a second mechanism that potentiates MyoD, i.e., by repressing the transcriptional activity of NF-κB, which is known to inhibit MyoD mRNA accumulation. IFRD1 represses the activity of NF-κBp65 by enhancing the HDAC-mediated deacetylation of the p65 subunit, by favoring the recruitment of HDAC3 to p65. In fact IFRD1 forms trimolecular complexes with p65 and HDAC3.[11]
Thus, IFRD1 can induce muscle regeneration acting as a pivotal regulator of the MyoD pathway through multiple mechanisms. Given the dramatic decrease of myogenic cells occurring in muscle degenerative pathologies such as Duchenne dystrophy, the ability of IFRD1 to potentiate the regenerative process suggests that IFRD1 might be a therapeutic target.
Interactionsedit
IFRD1 has been shown to interact with several proteins in the SIN3 complex including SIN3B, SAP30, NCOR1, and HDAC1.[13] Moreover, IFRD1 protein binds MyoD, MEF2C, HDAC4, HDAC3 and the p65 subunit of NF-κB, forming trimolecular complexes with HDAC3 and p65 NF-κB proteins.[11][12] IFRD1 protein also forms homodimers.[12]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000006652 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000001627 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abcBuanne P, Incerti B, Guardavaccaro D, Avvantaggiato V, Simeone A, Tirone F (Nov 1998). "Cloning of the human interferon-related developmental regulator (IFRD1) gene coding for the PC4 protein, a member of a novel family of developmentally regulated genes". Genomics. 51 (2): 233–42. doi:10.1006/geno.1998.5260. PMID 9722946.
^Tirone F, Shooter EM (March 1989). "Early gene regulation by nerve growth factor in PC12 cells: induction of an interferon-related gene". Proc. Natl. Acad. Sci. U.S.A. 86 (6): 2088–92. Bibcode:1989PNAS...86.2088T. doi:10.1073/pnas.86.6.2088. PMC286853. PMID 2467301.
^Gu Y, Harley IT, Henderson LB, Aronow BJ, Vietor I, Huber LA, Harley JB, Kilpatrick JR, Langefeld CD, Williams AH, Jegga AG, Chen J, Wills-Karp M, Arshad SH, Ewart SL, Thio CL, Flick LM, Filippi MD, Grimes HL, Drumm ML, Cutting GR, Knowles MR, Karp CL (April 2009). "Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease". Nature. 458 (7241): 1039–42. Bibcode:2009Natur.458.1039G. doi:10.1038/nature07811. PMC2841516. PMID 19242412.
^Montagnoli A, Guardavaccaro D, Starace G, Tirone F (October 1996). "Overexpression of the nerve growth factor-inducible PC3 immediate early gene is associated with growth inhibition". Cell Growth Differ. 7 (10): 1327–36. PMID 8891336.
^Vadivelu SK, Kurzbauer R, Dieplinger B, Zweyer M, Schafer R, Wernig A, Vietor I, Huber LA (April 2004). "Muscle regeneration and myogenic differentiation defects in mice lacking TIS7". Mol. Cell. Biol. 24 (8): 3514–25. doi:10.1128/mcb.24.8.3514-3525.2004. PMC381666. PMID 15060170.
^ abcdeMicheli L, Leonardi L, Conti F, Maresca G, Colazingari S, Mattei E, Lira SA, Farioli-Vecchioli S, Caruso M, Tirone F (February 2011). "PC4/Tis7/IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF-kappaB". J. Biol. Chem. 286 (7): 5691–707. doi:10.1074/jbc.M110.162842. PMC3037682. PMID 21127072.
^ abcdMicheli L, Leonardi L, Conti F, Buanne P, Canu N, Caruso M, Tirone F (March 2005). "PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C". Mol. Cell. Biol. 25 (6): 2242–59. doi:10.1128/MCB.25.6.2242-2259.2005. PMC1061592. PMID 15743821.
^Vietor I, Vadivelu SK, Wick N, Hoffman R, Cotten M, Seiser C, Fialka I, Wunderlich W, Haase A, Korinkova G, Brosch G, Huber LA (September 2002). "TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells". EMBO J. 21 (17): 4621–31. doi:10.1093/emboj/cdf461. PMC125408. PMID 12198164.
Further readingedit
Tirone F, Shooter EM (1989). "Early gene regulation by nerve growth factor in PC12 cells: induction of an interferon-related gene". Proc. Natl. Acad. Sci. U.S.A. 86 (6): 2088–92. Bibcode:1989PNAS...86.2088T. doi:10.1073/pnas.86.6.2088. PMC286853. PMID 2467301.
Varnum BC, Lim RW, Herschman HR (1989). "Characterization of TIS7, a gene induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate". Oncogene. 4 (10): 1263–5. PMID 2797820.
Guardavaccaro D, Ciotti MT, Schäfer BW, Montagnoli A, Tirone F (1995). "Inhibition of differentiation in myoblasts deprived of the interferon-related protein PC4". Cell Growth Differ. 6 (2): 159–69. PMID 7756174.
Guardavaccaro D, Montagnoli A, Ciotti MT, Gatti A, Lotti L, Di Lazzaro C, Torrisi MR, Tirone F (1994). "Nerve growth factor regulates the subcellular localization of the nerve growth factor-inducible protein PC4 in PC12 cells". J. Neurosci. Res. 37 (5): 660–74. doi:10.1002/jnr.490370514. PMID 8028043. S2CID 20845428.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Bonaldo MF, Lennon G, Soares MB (1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Ge H, Si Y, Roeder RG (1998). "Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation". EMBO J. 17 (22): 6723–9. doi:10.1093/emboj/17.22.6723. PMC1171017. PMID 9822615.
Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K (2002). "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants". Mol. Vis. 8: 205–20. PMID 12107410.
Vietor I, Vadivelu SK, Wick N, Hoffman R, Cotten M, Seiser C, Fialka I, Wunderlich W, Haase A, Korinkova G, Brosch G, Huber LA (2002). "TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells". EMBO J. 21 (17): 4621–31. doi:10.1093/emboj/cdf461. PMC125408. PMID 12198164.
Roth A, Gill R, Certa U (2003). "Temporal and spatial gene expression patterns after experimental stroke in a rat model and characterization of PC4, a potential regulator of transcription". Mol. Cell. Neurosci. 22 (3): 353–64. doi:10.1016/S1044-7431(02)00039-8. PMID 12691737. S2CID 2364009.
Imabayashi H, Mori T, Gojo S, Kiyono T, Sugiyama T, Irie R, Isogai T, Hata J, Toyama Y, Umezawa A (2003). "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis". Exp. Cell Res. 288 (1): 35–50. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
Micheli L, Leonardi L, Conti F, Buanne P, Canu N, Caruso M, Tirone F (2005). "PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C". Mol. Cell. Biol. 25 (6): 2242–59. doi:10.1128/MCB.25.6.2242-2259.2005. PMC1061592. PMID 15743821.
Vietor I, Kurzbauer R, Brosch G, Huber LA (2005). "TIS7 regulation of the beta-catenin/Tcf-4 target gene osteopontin (OPN) is histone deacetylase-dependent". J. Biol. Chem. 280 (48): 39795–801. doi:10.1074/jbc.M509836200. PMID 16204248.
Guo H, Gao C, Mi Z, Zhang J, Kuo PC (2007). "Characterization of the PC4 binding domain and its interactions with HNF4alpha". J. Biochem. 141 (5): 635–40. doi:10.1093/jb/mvm066. PMID 17317687.
December 15, 2023
ifrd1, interferon, related, developmental, regulator, protein, that, humans, encoded, gene, gene, expressed, mostly, neutrophils, skeletal, cardiac, muscle, brain, pancreas, mouse, homolog, genes, interferon, related, developmental, regulator, gene, their, pro. Interferon related developmental regulator 1 is a protein that in humans is encoded by the IFRD1 gene 5 6 The gene is expressed mostly in neutrophils skeletal and cardiac muscle the brain and the pancreas 5 6 The rat and the mouse homolog genes of interferon related developmental regulator 1 gene and their proteins are also known with the name PC4 7 and Tis21 respectively IFRD1 is member of a gene family that comprises a second gene IFRD2 also known as SKmc15 5 6 IFRD1IdentifiersAliasesIFRD1 PC4 TIS7 interferon related developmental regulator 1External IDsOMIM 603502 MGI 1316717 HomoloGene 31043 GeneCards IFRD1Gene location Human Chr Chromosome 7 human 1 Band7q31 1Start112 422 887 bp 1 End112 481 017 bp 1 Gene location Mouse Chr Chromosome 12 mouse 2 Band12 B1 12 18 06 cMStart40 251 566 bp 2 End40 298 503 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inbody of pancreasjejunal mucosagerminal epitheliumvena cavaamniotic fluidgastric mucosasaphenous veinright lungascending aortapopliteal arteryTop expressed insecondary oocyteparotid glandlipsuperior cervical ganglionintercostal musclecumulus cellduodenumdigastric muscleislet of LangerhansjejunumMore reference expression dataBioGPSMore reference expression dataOrthologsSpeciesHumanMouseEntrez347515982EnsemblENSG00000006652ENSMUSG00000001627UniProtO00458P19182RefSeq mRNA NM 001007245NM 001197079NM 001197080NM 001550NM 013562RefSeq protein NP 001007246NP 001184008NP 001184009NP 001541NP 038590Location UCSC Chr 7 112 42 112 48 MbChr 12 40 25 40 3 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Clinical significance 2 Inducer of muscle regeneration 3 Interactions 4 References 5 Further readingClinical significance editIFRD1 has been identified as a modifier gene for cystic fibrosis lung disease In humans neutrophil effector function is dependent on the type of IRFD1 polymorphism present in the individual Human and mouse data both indicate that IFRD1 has a sizable impact on cystic fibrosis pathogenesis by regulating neutrophil effector function 8 Inducer of muscle regeneration editIFRD1 also known as PC4 or Tis7 see above participates to the process of skeletal muscle cell differentiation In fact inhibition of IFRD1 function in C2C12 myoblasts by antisense IFRD1 cDNA transfection or microinjection of anti IFRD1 antibodies prevents their morphological and biochemical differentiation by inhibiting the expression of MyoD and myogenin key master genes of muscle development 9 A role for IFRD1 in muscle differentiation has been observed also in vivo Muscles from mice lacking IFRD1 display decreased protein and mRNA levels of MyoD and myogenin and after muscle crash damage in young mice there was a delay in regeneration 10 Recently it has been shown that upregulation of IFRD1 in vivo in injured muscle potentiates muscle regeneration by increasing the production of staminal muscle cells satellite cells 11 The underlying molecular mechanism lies in the ability of IFRD1 to cooperate with MyoD at inducing the transcriptional activity of MEF2C This relies on the ability of IFRD1 to bind selectively MEF2C thus inhibiting its interaction with HDAC4 11 12 Therefore IFRD1 appears to act as a positive cofactor of MyoD 11 12 More recently it has been shown that IFRD1 potentiates muscle regeneration by a second mechanism that potentiates MyoD i e by repressing the transcriptional activity of NF kB which is known to inhibit MyoD mRNA accumulation IFRD1 represses the activity of NF kB p65 by enhancing the HDAC mediated deacetylation of the p65 subunit by favoring the recruitment of HDAC3 to p65 In fact IFRD1 forms trimolecular complexes with p65 and HDAC3 11 Thus IFRD1 can induce muscle regeneration acting as a pivotal regulator of the MyoD pathway through multiple mechanisms Given the dramatic decrease of myogenic cells occurring in muscle degenerative pathologies such as Duchenne dystrophy the ability of IFRD1 to potentiate the regenerative process suggests that IFRD1 might be a therapeutic target Interactions editIFRD1 has been shown to interact with several proteins in the SIN3 complex including SIN3B SAP30 NCOR1 and HDAC1 13 Moreover IFRD1 protein binds MyoD MEF2C HDAC4 HDAC3 and the p65 subunit of NF kB forming trimolecular complexes with HDAC3 and p65 NF kB proteins 11 12 IFRD1 protein also forms homodimers 12 References edit a b c GRCh38 Ensembl release 89 ENSG00000006652 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000001627 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c Buanne P Incerti B Guardavaccaro D Avvantaggiato V Simeone A Tirone F Nov 1998 Cloning of the human interferon related developmental regulator IFRD1 gene coding for the PC4 protein a member of a novel family of developmentally regulated genes Genomics 51 2 233 42 doi 10 1006 geno 1998 5260 PMID 9722946 a b c Entrez Gene IFRD1 interferon related developmental regulator 1 Tirone F Shooter EM March 1989 Early gene regulation by nerve growth factor in PC12 cells induction of an interferon related gene Proc Natl Acad Sci U S A 86 6 2088 92 Bibcode 1989PNAS 86 2088T doi 10 1073 pnas 86 6 2088 PMC 286853 PMID 2467301 Gu Y Harley IT Henderson LB Aronow BJ Vietor I Huber LA Harley JB Kilpatrick JR Langefeld CD Williams AH Jegga AG Chen J Wills Karp M Arshad SH Ewart SL Thio CL Flick LM Filippi MD Grimes HL Drumm ML Cutting GR Knowles MR Karp CL April 2009 Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease Nature 458 7241 1039 42 Bibcode 2009Natur 458 1039G doi 10 1038 nature07811 PMC 2841516 PMID 19242412 Montagnoli A Guardavaccaro D Starace G Tirone F October 1996 Overexpression of the nerve growth factor inducible PC3 immediate early gene is associated with growth inhibition Cell Growth Differ 7 10 1327 36 PMID 8891336 Vadivelu SK Kurzbauer R Dieplinger B Zweyer M Schafer R Wernig A Vietor I Huber LA April 2004 Muscle regeneration and myogenic differentiation defects in mice lacking TIS7 Mol Cell Biol 24 8 3514 25 doi 10 1128 mcb 24 8 3514 3525 2004 PMC 381666 PMID 15060170 a b c d e Micheli L Leonardi L Conti F Maresca G Colazingari S Mattei E Lira SA Farioli Vecchioli S Caruso M Tirone F February 2011 PC4 Tis7 IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF kappaB J Biol Chem 286 7 5691 707 doi 10 1074 jbc M110 162842 PMC 3037682 PMID 21127072 a b c d Micheli L Leonardi L Conti F Buanne P Canu N Caruso M Tirone F March 2005 PC4 coactivates MyoD by relieving the histone deacetylase 4 mediated inhibition of myocyte enhancer factor 2C Mol Cell Biol 25 6 2242 59 doi 10 1128 MCB 25 6 2242 2259 2005 PMC 1061592 PMID 15743821 Vietor I Vadivelu SK Wick N Hoffman R Cotten M Seiser C Fialka I Wunderlich W Haase A Korinkova G Brosch G Huber LA September 2002 TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells EMBO J 21 17 4621 31 doi 10 1093 emboj cdf461 PMC 125408 PMID 12198164 Further reading editTirone F Shooter EM 1989 Early gene regulation by nerve growth factor in PC12 cells induction of an interferon related gene Proc Natl Acad Sci U S A 86 6 2088 92 Bibcode 1989PNAS 86 2088T doi 10 1073 pnas 86 6 2088 PMC 286853 PMID 2467301 Varnum BC Lim RW Herschman HR 1989 Characterization of TIS7 a gene induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate Oncogene 4 10 1263 5 PMID 2797820 Guardavaccaro D Ciotti MT Schafer BW Montagnoli A Tirone F 1995 Inhibition of differentiation in myoblasts deprived of the interferon related protein PC4 Cell Growth Differ 6 2 159 69 PMID 7756174 Guardavaccaro D Montagnoli A Ciotti MT Gatti A Lotti L Di Lazzaro C Torrisi MR Tirone F 1994 Nerve growth factor regulates the subcellular localization of the nerve growth factor inducible protein PC4 in PC12 cells J Neurosci Res 37 5 660 74 doi 10 1002 jnr 490370514 PMID 8028043 S2CID 20845428 Maruyama K Sugano S 1994 Oligo capping a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides Gene 138 1 2 171 4 doi 10 1016 0378 1119 94 90802 8 PMID 8125298 Bonaldo MF Lennon G Soares MB 1996 Normalization and subtraction two approaches to facilitate gene discovery Genome Res 6 9 791 806 doi 10 1101 gr 6 9 791 PMID 8889548 Suzuki Y Yoshitomo Nakagawa K Maruyama K Suyama A Sugano S 1997 Construction and characterization of a full length enriched and a 5 end enriched cDNA library Gene 200 1 2 149 56 doi 10 1016 S0378 1119 97 00411 3 PMID 9373149 Ge H Si Y Roeder RG 1998 Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation EMBO J 17 22 6723 9 doi 10 1093 emboj 17 22 6723 PMC 1171017 PMID 9822615 Wistow G Bernstein SL Wyatt MK Fariss RN Behal A Touchman JW Bouffard G Smith D Peterson K 2002 Expressed sequence tag analysis of human RPE choroid for the NEIBank Project over 6000 non redundant transcripts novel genes and splice variants Mol Vis 8 205 20 PMID 12107410 Vietor I Vadivelu SK Wick N Hoffman R Cotten M Seiser C Fialka I Wunderlich W Haase A Korinkova G Brosch G Huber LA 2002 TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells EMBO J 21 17 4621 31 doi 10 1093 emboj cdf461 PMC 125408 PMID 12198164 Roth A Gill R Certa U 2003 Temporal and spatial gene expression patterns after experimental stroke in a rat model and characterization of PC4 a potential regulator of transcription Mol Cell Neurosci 22 3 353 64 doi 10 1016 S1044 7431 02 00039 8 PMID 12691737 S2CID 2364009 Imabayashi H Mori T Gojo S Kiyono T Sugiyama T Irie R Isogai T Hata J Toyama Y Umezawa A 2003 Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large scale cDNA analysis Exp Cell Res 288 1 35 50 doi 10 1016 S0014 4827 03 00130 7 PMID 12878157 Micheli L Leonardi L Conti F Buanne P Canu N Caruso M Tirone F 2005 PC4 coactivates MyoD by relieving the histone deacetylase 4 mediated inhibition of myocyte enhancer factor 2C Mol Cell Biol 25 6 2242 59 doi 10 1128 MCB 25 6 2242 2259 2005 PMC 1061592 PMID 15743821 Vietor I Kurzbauer R Brosch G Huber LA 2005 TIS7 regulation of the beta catenin Tcf 4 target gene osteopontin OPN is histone deacetylase dependent J Biol Chem 280 48 39795 801 doi 10 1074 jbc M509836200 PMID 16204248 Guo H Gao C Mi Z Zhang J Kuo PC 2007 Characterization of the PC4 binding domain and its interactions with HNF4alpha J Biochem 141 5 635 40 doi 10 1093 jb mvm066 PMID 17317687 Retrieved from https en wikipedia org w index php title IFRD1 amp oldid 1142711021, wikipedia, wiki, book, books, library,
