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Gene Review

RCC1  -  regulator of chromosome condensation 1

Homo sapiens

Synonyms: CHC1, Cell cycle regulatory protein, Chromosome condensation protein 1, RCC1-I, Regulator of chromosome condensation, ...
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Disease relevance of RCC1


High impact information on RCC1

  • Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1) [5].
  • The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase [6].
  • We propose that RCC1 generates a high local concentration of Ran-GTP around chromatin which in turn induces the local nucleation of microtubules [7].
  • One known regulator, the protein RCC1 (refs 12, 13), interacts with Ran to catalyse guanine nucleotide exchange, and both RCC1 and Ran are components of an intrinsic checkpoint control that prevents the premature initiation of mitosis [8].
  • Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4 [8].

Chemical compound and disease context of RCC1


Biological context of RCC1


Anatomical context of RCC1

  • The product of the gene RCC1 (regulator of chromosome condensation) in a BHK cell line is involved in the control of mitotic events [13].
  • HeLa cell RCC1 is complexed to a protein of Mr 25K [13].
  • Thus, RCC1 protein locates on the chromatin and is not a component of the nuclear matrix [17].
  • Surprisingly, we found that neither Xenopus ovarian cytosol nor a mixture of recombinant import factors (karyopherin alpha2, karyopherin beta1, Ran, and p10/NTF2) were able to support the import of pA-RCC1 into the nuclei of digitonin-permeabilized cells [18].
  • The steepness of the RanGTP gradient appears limited by both the cytoplasmic RanGAP concentration and the imperfect retention of nuclear RanGTP by nuclear pore complexes (NPCs), but not by the nucleotide exchange activity of RCC1 [19].

Associations of RCC1 with chemical compounds

  • The RCC1 protein, a regulator for the onset of chromosome condensation locates in the nucleus and binds to DNA [17].
  • Crystals of human RCC1 suitable for X-ray analysis have been obtained using the seeding technique in hanging drops with sodium citrate as a precipitant [20].
  • This homozygous G669A mutation in exon 4 is predicted to result in a tyrosine substitution at cysteine 156 of the RCC1 (regulator of chromatin condensation)-like domain, encoding a putative guanine exchange factor for Ran guanosine triphosphatase, leading to a loss of ALS2 function due to instability of mutant protein [21].
  • Leptomycin B, which inhibits Crm1/RanGTP-dependent nuclear export, significantly increased the mobility of RCC1 as did high levels of actinomycin D (to inhibit RNA polymerases I, II, and III) or alpha-amanitin (to inhibit RNA polymerases II and III) as well as energy depletion [22].
  • Further sudies on the role of the RCC1-like domain in the visual Cascade and additional findings of related proteins in the retina or even other organs, will give us a more precise understanding of this protein [23].

Physical interactions of RCC1

  • This interaction was stimulated by the addition of Ran; moreover, Ran.GDP, Ran.GTP, and Ran without nucleotide could all stimulate complex formation between RanBP3 and RCC1 even though binding of Ran.GDP to RanBP3 alone was undetectable [24].
  • We find that RCC1 binds directly to mononucleosomes and to histones H2A and H2B [14].
  • The C terminus of the nuclear RAN/TC4 GTPase stabilizes the GDP-bound state and mediates interactions with RCC1, RAN-GAP, and HTF9A/RANBP1 [25].
  • RRAG A (Rag A)/Gtr1p is a member of the Ras-like small G protein family that genetically interacts with RCC1, a guanine nucleotide exchange factor for RanGTPase [26].

Regulatory relationships of RCC1


Other interactions of RCC1


Analytical, diagnostic and therapeutic context of RCC1


  1. Novel deletion spanning RCC1-like domain of RPGR in Japanese X-linked retinitis pigmentosa family. Jin, Z.B., Liu, X.Q., Uchida, A., Vervoort, R., Morishita, K., Hayakawa, M., Murakami, A., Matsumoto, N., Niikawa, N., Nao-i, N. Mol. Vis. (2005) [Pubmed]
  2. Distinctive cell cycle regulatory protein profiles by adenovirus delivery of p53 in human papillomavirus-associated cancer cells. Jin, H.S., Bae, S.M., Kim, Y.W., Lee, J.M., Namkoong, S.E., Han, B.D., Lee, Y.J., Kim, C.K., Chun, H.J., Ahn, W.S. Int. J. Gynecol. Cancer (2006) [Pubmed]
  3. Replication of herpes simplex virus type 1 DNA is inhibited in a temperature-sensitive mutant of BHK-21 cells lacking RCC1 (regulator of chromosome condensation) and virus DNA remains linear. Umene, K., Nishimoto, T. J. Gen. Virol. (1996) [Pubmed]
  4. Cell cycle regulatory gene abnormalities are important determinants of leukemogenesis and disease biology in adult acute lymphoblastic leukemia. Stock, W., Tsai, T., Golden, C., Rankin, C., Sher, D., Slovak, M.L., Pallavicini, M.G., Radich, J.P., Boldt, D.H. Blood (2000) [Pubmed]
  5. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Renault, L., Kuhlmann, J., Henkel, A., Wittinghofer, A. Cell (2001) [Pubmed]
  6. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Meindl, A., Dry, K., Herrmann, K., Manson, F., Ciccodicola, A., Edgar, A., Carvalho, M.R., Achatz, H., Hellebrand, H., Lennon, A., Migliaccio, C., Porter, K., Zrenner, E., Bird, A., Jay, M., Lorenz, B., Wittwer, B., D'Urso, M., Meitinger, T., Wright, A. Nat. Genet. (1996) [Pubmed]
  7. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Carazo-Salas, R.E., Guarguaglini, G., Gruss, O.J., Segref, A., Karsenti, E., Mattaj, I.W. Nature (1999) [Pubmed]
  8. Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4. Coutavas, E., Ren, M., Oppenheim, J.D., D'Eustachio, P., Rush, M.G. Nature (1993) [Pubmed]
  9. A novel retinoid-related molecule inhibits pancreatic cancer cell proliferation by a retinoid receptor independent mechanism via suppression of cell cycle regulatory protein function and induction of caspase-associated apoptosis. Balasubramanian, S., Chandraratna, R.A., Eckert, R.L. Oncogene (2005) [Pubmed]
  10. Cyclin D1 expression is dependent on estrogen receptor function in tamoxifen-resistant breast cancer cells. Kilker, R.L., Hartl, M.W., Rutherford, T.M., Planas-Silva, M.D. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  11. Retinoic acid-induced RB (retinoblastoma) hypophosphorylation enhanced by CGP 52411 (4,5-dianilinophthalimide), an EGF family tyrosine kinase receptor inhibitor. Yen, A., Soong, S. Eur. J. Cell Biol. (1996) [Pubmed]
  12. Roscovitine regulates invasive breast cancer cell (MDA-MB231) proliferation and survival through cell cycle regulatory protein cdk5. Goodyear, S., Sharma, M.C. Exp. Mol. Pathol. (2007) [Pubmed]
  13. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Bischoff, F.R., Ponstingl, H. Nature (1991) [Pubmed]
  14. Chromatin docking and exchange activity enhancement of RCC1 by histones H2A and H2B. Nemergut, M.E., Mizzen, C.A., Stukenberg, T., Allis, C.D., Macara, I.G. Science (2001) [Pubmed]
  15. Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation. Ohtsubo, M., Kai, R., Furuno, N., Sekiguchi, T., Sekiguchi, M., Hayashida, H., Kuma, K., Miyata, T., Fukushige, S., Murotsu, T. Genes Dev. (1987) [Pubmed]
  16. Phosphorylation of RCC1 in mitosis is essential for producing a high RanGTP concentration on chromosomes and for spindle assembly in mammalian cells. Li, H.Y., Zheng, Y. Genes Dev. (2004) [Pubmed]
  17. The RCC1 protein, a regulator for the onset of chromosome condensation locates in the nucleus and binds to DNA. Ohtsubo, M., Okazaki, H., Nishimoto, T. J. Cell Biol. (1989) [Pubmed]
  18. The nuclear import of RCC1 requires a specific nuclear localization sequence receptor, karyopherin alpha3/Qip. Talcott, B., Moore, M.S. J. Biol. Chem. (2000) [Pubmed]
  19. Characterization of Ran-driven cargo transport and the RanGTPase system by kinetic measurements and computer simulation. Görlich, D., Seewald, M.J., Ribbeck, K. EMBO J. (2003) [Pubmed]
  20. Crystallization and preliminary X-ray analysis of human RCC1, the regulator of chromosome condensation. Renault, L., Nassar, N., Wittinghofer, A., Roth, M., Vetter, I.R. Acta Crystallogr. D Biol. Crystallogr. (1999) [Pubmed]
  21. Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis. Eymard-Pierre, E., Yamanaka, K., Haeussler, M., Kress, W., Gauthier-Barichard, F., Combes, P., Cleveland, D.W., Boespflug-Tanguy, O. Ann. Neurol. (2006) [Pubmed]
  22. The dynamic association of RCC1 with chromatin is modulated by Ran-dependent nuclear transport. Cushman, I., Stenoien, D., Moore, M.S. Mol. Biol. Cell (2004) [Pubmed]
  23. RCC1-like domain and ORF15: essentials in RPGR gene. Jin, Z.B., Hayakawa, M., Murakami, A., Nao-i, N. Adv. Exp. Med. Biol. (2006) [Pubmed]
  24. Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor. Nemergut, M.E., Lindsay, M.E., Brownawell, A.M., Macara, I.G. J. Biol. Chem. (2002) [Pubmed]
  25. The C terminus of the nuclear RAN/TC4 GTPase stabilizes the GDP-bound state and mediates interactions with RCC1, RAN-GAP, and HTF9A/RANBP1. Richards, S.A., Lounsbury, K.M., Macara, I.G. J. Biol. Chem. (1995) [Pubmed]
  26. A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D. Sekiguchi, T., Todaka, Y., Wang, Y., Hirose, E., Nakashima, N., Nishimoto, T. J. Biol. Chem. (2004) [Pubmed]
  27. RanBP1, a Ras-like nuclear G protein binding to Ran/TC4, inhibits RCC1 via Ran/TC4. Hayashi, N., Yokoyama, N., Seki, T., Azuma, Y., Ohba, T., Nishimoto, T. Mol. Gen. Genet. (1995) [Pubmed]
  28. The mechanism of nuclear export of Smad3 involves exportin 4 and Ran. Kurisaki, A., Kurisaki, K., Kowanetz, M., Sugino, H., Yoneda, Y., Heldin, C.H., Moustakas, A. Mol. Cell. Biol. (2006) [Pubmed]
  29. The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. Wu, Y.J., Muldoon, L.L., Neuwelt, E.A. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  30. Cell cycle regulation and induction of apoptosis by IL-6 variants on the multiple myeloma cell line XG-1. Petrucci, M.T., Ricciardi, M.R., Ariola, C., Gregorj, C., Ribersani, M., Savino, R., Ciliberto, G., Tafuri, A. Ann. Hematol. (1999) [Pubmed]
  31. The cyclin-dependent kinase 2 inhibitor down-regulates interleukin-1beta-mediated induction of cyclooxygenase-2 expression in human lung carcinoma cells. Mukhopadhyay, P., Ali, M.A., Nandi, A., Carreon, P., Choy, H., Saha, D. Cancer Res. (2006) [Pubmed]
  32. The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Linari, M., Ueffing, M., Manson, F., Wright, A., Meitinger, T., Becker, J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  33. The human CHC1 gene encoding RCC1 (regulator of chromosome condensation) (CHC1) is localized to human chromosome 1p36.1. Nishimoto, T., Seino, H., Seki, N., Hori, T.A. Genomics (1994) [Pubmed]
  34. Immunolymphoscintigraphy for the detection of lymph node metastases from breast cancer. Tjandra, J.J., Russell, I.S., Collins, J.P., Andrews, J.T., Lichtenstein, M., Binns, D., McKenzie, I.F. Cancer Res. (1989) [Pubmed]
  35. Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression. Siavoshian, S., Segain, J.P., Kornprobst, M., Bonnet, C., Cherbut, C., Galmiche, J.P., Blottière, H.M. Gut (2000) [Pubmed]
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