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Gene Review

IFRD1  -  interferon-related developmental regulator 1

Homo sapiens

Synonyms: Interferon-related developmental regulator 1, Nerve growth factor-inducible protein PC4, PC4, TIS7
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Disease relevance of IFRD1


High impact information on IFRD1

  • We investigated the early differentiative phase and identified a gene, PC4, rapidly and transiently induced by NGF in PC12 cells [2].
  • PC4 is expressed in proliferating and differentiating tissues, such as amnion, placenta, and brain at embryonic day 13 [2].
  • PC4 is predominantly associated with the chromatin throughout the stages of cell cycle and is broadly distributed on the mitotic chromosome arms in a punctate manner except for the centromere [3].
  • Knocking down of PC4 up-regulates several genes, leading to the G(2)/M checkpoint arrest of cell cycle, which suggests its physiological role as a chromatin-compacting protein [3].
  • Silencing of PC4 expression in HeLa cells results in chromatin decompaction, as evidenced by the increase in MNase accessibility [3].

Biological context of IFRD1

  • The mapping assignment of human IFRD1 to chromosome 7q22-q31 was retrieved from the UniGene database maintained at NCBI [4].
  • The immediate early gene (IEG) PC4, which encodes a protein related to gamma interferon, is activated at the onset of the neuronal differentiation induced by nerve growth factor (NGF) in PC12 cells [5].
  • This transient down-regulation of PC4 expression in C2C12 myoblasts is prevented by transforming growth factor beta, a molecule which inhibits the differentiation of muscle [6].
  • The existence within the PC4 protein of a consensus sequence for the addition of myristic acid and of a putative sequence for the nuclear localization suggests possible mechanisms for the NGF-dependent redistribution [5].
  • Sense and antisense PC4 cDNA transfection strategies in C2C12 cells were then used to clarify the role of PC4 in muscle differentiation [6].

Anatomical context of IFRD1

  • Inhibition of differentiation in myoblasts deprived of the interferon-related protein PC4 [6].
  • After longer NGF treatment, PC4 disappears from the plasma membrane and appears in the nucleus, with reduced cytoplasmic expression [5].
  • Here we report that PC4 mRNA is also expressed in the myoblast C2C12 cell line and is regulated during differentiation; its expression decreases within 6 h from the onset of differentiation, attains a minimum after 12 h, and returns to basal level within 36 h [6].

Associations of IFRD1 with chemical compounds


Analytical, diagnostic and therapeutic context of IFRD1

  • Immunofluorescence, electron microscopy and subfractionation studies indicate that the PC4 immunoreactivity is localized in the cytoplasm of PC12 cells, where it is increased transiently by NGF within 3 hr of treatment [5].
  • It selectively interacts with core histones H3 and H2B; this interaction is essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and atomic force microscopy (AFM) [3].


  1. The human homolog of the rodent immediate early response genes, PC4 and TIS7, resides in the lung cancer tumor suppressor gene region on chromosome 3p21. Latif, F., Duh, F.M., Bader, S., Sekido, Y., Li, H., Geil, L., Zbar, B., Minna, J.D., Lerman, M.I. Hum. Genet. (1997) [Pubmed]
  2. Early gene regulation by nerve growth factor in PC12 cells: induction of an interferon-related gene. Tirone, F., Shooter, E.M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  3. Transcriptional Coactivator PC4, a Chromatin-Associated Protein, Induces Chromatin Condensation. Das, C., Hizume, K., Batta, K., Kumar, B.R., Gadad, S.S., Ganguly, S., Lorain, S., Verreault, A., Sadhale, P.P., Takeyasu, K., Kundu, T.K. Mol. Cell. Biol. (2006) [Pubmed]
  4. 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. Buanne, P., Incerti, B., Guardavaccaro, D., Avvantaggiato, V., Simeone, A., Tirone, F. Genomics (1998) [Pubmed]
  5. Nerve growth factor regulates the subcellular localization of the nerve growth factor-inducible protein PC4 in PC12 cells. Guardavaccaro, D., Montagnoli, A., Ciotti, M.T., Gatti, A., Lotti, L., Di Lazzaro, C., Torrisi, M.R., Tirone, F. J. Neurosci. Res. (1994) [Pubmed]
  6. Inhibition of differentiation in myoblasts deprived of the interferon-related protein PC4. Guardavaccaro, D., Ciotti, M.T., Schäfer, B.W., Montagnoli, A., Tirone, F. Cell Growth Differ. (1995) [Pubmed]
  7. The VP16 Activation Domain Establishes an Active Mediator Lacking CDK8 in Vivo. Uhlmann, T., Boeing, S., Lehmbacher, M., Meisterernst, M. J. Biol. Chem. (2007) [Pubmed]
  8. Differentially expressed genes in hemocytes of Vibrio harveyi-challenged shrimp Penaeus monodon. Somboonwiwat, K., Supungul, P., Rimphanitchayakit, V., Aoki, T., Hirono, I., Tassanakajon, A. J. Biochem. Mol. Biol. (2006) [Pubmed]
  9. Gradual phosphorylation regulates PC4 coactivator function. Jonker, H.R., Wechselberger, R.W., Pinkse, M., Kaptein, R., Folkers, G.E. FEBS J. (2006) [Pubmed]
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