Interferon-binding development regulator 1 - a protein encoded in humans by the IFRD1 gene . [1] [2] This gene is expressed mainly in neutrophils , skeletal and cardiac muscles, brain, pancreas. [1] [2] In rats and mice, the homologues of these genes (and their proteins) are also known as PC4 [3] and Tis21, respectively. IFRD1 is a member of the gene family containing the second gene, IFRD2, also known as SKmc15. [1] [2]
Interferon binding development regulator 1 | |||||||||||||
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Symbol | ; PC4; TIS7 | ||||||||||||
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Content
Clinical value
IFRD1 was identified as a gene modifier for lung disease such as cystic fibrosis . [four]
Induction of muscle regeneration
IFRD1 (also known as PC4 or Tis7, see above) is involved in the differentiation of skeletal muscle cells. In fact, inhibition of the function of IFRD1 C2C12 myoblasts prevents their morphological and biochemical differentiation by inhibiting the expression of MyoD and myogenin , the master key of muscle development genes. [5] Under natural conditions, the role of IFRD1 in muscle differentiation is also observed. The muscles of mice lacking IFRD1 show a decrease in protein, mRNA level, MyoD myogenin, and regeneration delay after muscle damage in young mice. [6]
Recently, it has been found that the positive regulation of IFRD1 in vivo in injured muscle enhances its regeneration by increasing the production of staminate muscle cells (satellite cells). [7] The basic molecular mechanism lies in the ability of IFRD1 to collaborate with MyoD in inducing MEF2C transcriptional activity. This depends on the ability of IFRD1 to selectively bind to MEF2C, thus hindering its interaction with HDAC4. [7] [8] Thus, IFRD1 appears to act as a positive cofactor for MyoD. [7] [8] Recently, it has been found that IFRD1 potentiates muscle regeneration using a second mechanism that enhances MyoD, that is, by suppressing the transcriptional activity of NF-kB , which is known to inhibit MyoD accumulation in mRNA. IFRD1 suppresses pF65 NF-kB activity by increasing the HDAC-mediated deacetylation of the p65 subunit, preferring HDAC3 recruitment for p65. In fact, IFRD1 forms trimolecular complexes with p65 and HDAC3. [7]
Thus, IFRD1 can cause muscle regeneration, acting as a key regulator of MyoD through several mechanisms. Given the sharp decline in myogenic cells that occur in degenerative muscle diseases such as Duchenne dystrophy ( eng. Duchenne dystrophy ), the ability of IFRD1 to potentiate the regeneration process suggests that IFRD1 may be the goal of therapy.
Interactions
IFRD1 has been shown to interact with several proteins of the SIN3 complex, including SIN3B , SAP30 , NCOR1 and HDAC1 . [9] In addition, IFRD1 binds to MyoD , Mef2c , HDAC4 , HDAC3 and the p65 subunit of the NF-kB factor, forming trimolecular complexes with HDAC3 and p65 of the NF-kB proteins. [10] [11] The IFRD1 protein also forms homodimers . [eight]
Notes
- 2 1 2 3 Buanne P., Incerti B., Guardavaccaro D., Avvantaggiato V., Simeone A., Tirone F. Cloning of the human interferon-related developmental regulator (IFRD1) novel family of developmentally regulated genes (eng.) // Genomics: journal. - 1998. - November ( vol. 51 , no. 2 ). - P. 233-224 . - DOI : 10.1006 / geno.1998.5260 . - PMID 9722946 .
- 2 1 2 3 Entrez Gene: IFRD1 interferon-related developmental regulator 1 .
- Ir Tirone F., Shooter EM : Induction of an interferon-related gene (In English) // Proceedings of the United States of America : journal. - 1989. - March ( vol. 86 , no. 6 ). - P. 2088-2092 . - DOI : 10.1073 / pnas.86.6.2088 . - 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 Identification of IFRD1 as a modifier for cystic fibrosis lung disease (Eng.) // Nature: journal. - 2009. - April ( vol. 458 , no. 7241 ). - P. 1039-1042 . - DOI : 10.1038 / nature07811 . - PMID 19242412 .
- ↑ Montagnoli, A., Guardavaccaro, D., Starace, G., Tirone F. Overexpression of the nerve growth factor-inducible PC3, Molecular Cancer Research : journal. - 1996. - October ( vol. 7 , no. 10 ). - P. 1327-1336 . - PMID 8891336 .
- ↑ Vadivelu SK, Kurzbauer R., Dieplinger B., Zweyer M., Schafer R., Wernig A., Vietor I., Huber LA Muscle regeneration and myogenic differences // Molecular and Cellular Biology : journal. - 2004. - April ( vol. 24 , no. 8 ). - P. 3514–3525 . - DOI : 10.1128 / mcb.24.8.3514-3525.2004 . - PMID 15060170 .
- ↑ 1 2 3 4 Micheli L., Leonardi L., Conti F., Maresca G., Colazingari S., Mattei E., Lira SA, Farioli-Vecchioli S., Caruso M., Tirone F. PC4 / Tis7 / IFRD1 stimulation of myoD and NF-kappaB (English) // Journal of Biological Chemistry : journal. - 2011. - February ( vol. 286 , no. 7 ). - P. 5691-5707 . - DOI : 10.1074 / jbc.M110.162842 . - PMID 21127072 .
- 2 1 2 3 Micheli L., Leonardi L., Conti F., Buanne P., Canu N., Caruso M., and Tirone F. PC4 coactivates myoD by relieving the myocyte enhancer factor 2C (English .) // Molecular and Cellular Biology : journal. - 2005. - March ( vol. 25 , no. 6 ). - P. 2242-2259 . - DOI : 10.1128 / MCB.25.6.2242-2259.2005 . - 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 TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells (English) // The EMBO Journal : journal. - 2002. - September ( vol. 21 , no. 17 ). - P. 4621-4631 . - DOI : 10.1093 / emboj / cdf461 . - PMID 12198164 .
- ↑ Micheli L., Leonardi L., Conti F., Maresca G., Colazingari S., Mattei E., Lira SA, Farioli-Vecchioli S., Caruso M., Tirone F. PC4 / Tis7 / IFRD1 stimulated skeletal muscle regeneration and is involved in myoblast differentiation of mydoD and NF-kappaB (Eng.) // Journal of Biological Chemistry : journal. - 2011. - February ( vol. 286 , no. 7 ). - P. 5691-5707 . - DOI : 10.1074 / jbc.M110.162842 . - PMID 21127072 .
- ↑ Micheli L., Leonardi L., Conti F., Buanne P., Canu N., Caruso M., Tirone F. PC4 coactivates MyoD by releasing the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C (English) / / Molecular and Cellular Biology : journal. - 2005. - March ( vol. 25 , no. 6 ). - P. 2242-2259 . - DOI : 10.1128 / MCB.25.6.2242-2259.2005 . - PMID 15743821 .
Literature
- Tirone F. Shooter EM: Induction of the Interferon -Related Gene (Eng.) // Proceedings of the United States of America : journal. - 1989. - Vol. 86 , no. 6 - P. 2088-2092 . - DOI : 10.1073 / pnas.86.6.2088 . - PMID 2467301 .
- Varnum BC, Lim RW, Herschman HR Characterization of TIS7, a gene induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate (English) // Oncogene : journal. - 1989. - Vol. 4 , no. 10 - P. 1263-1265 . - PMID 2797820 .
- Guardavaccaro D., Ciotti MT, Schäfer BW, Montagnoli A., Tirone F. Inhibition of the interferon-related protein PC4 (Eng.) // Molecular Cancer Research : journal. - 1995. - Vol. 6 , no. 2 - P. 159-169 . - PMID 7756174 .
- Guardavaccaro D., Montagnoli A., Ciotti MT, Gatti A., Lotti L., Di Lazzaro C., Torrisi MR, Tirone F. Nerve growth factor regression -inducible protein PC4 in PC12 cells ( English) // Journal of Neuroscience Research : journal. - 1994. - Vol. 37 , no. 5 - P. 660-674 . - DOI : 10.1002 / jnr.490370514 . - PMID 8028043 .
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- Vietor I., Kurzbauer R., Brosch G., Huber LA TIS 7 regulation of the beta-catenin / Tcf-4 target gene osteopontin (OPN) is a histone deacetylase-dependent (Eng.) // Journal of Biological Chemistry : journal. - 2005. - Vol. 280 , no. 48 . - P. 39795—39801 . - DOI : 10.1074 / jbc.M509836200 . - PMID 16204248 .
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