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Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells

Oncogene volume 21, pages 3112–3120 (2002)Cite this article

Abstract

Ini1/hsnf5 gene encodes INI1 protein, a chromatin remodeling factor associated with the SWI/SNF complex. In yeast, this complex modifies chromatin condensation to coactivate various transcriptional factors. However, in human, little is known about the SWI/SNF complex and INI1. To elucidate cellular functions of ini1, we constructed a recombinant adenovirus (AdexHA-INI1) capable of overexpressing INI1 in ini1-deficient cells. AdexHA-INI1 produced intranuclear INI1 in three ini1-deficient cell lines, changed their morphology, and decreased the proportion of viable cells. Flow cytometry and a BrdU incorporation assay showed that after the infection, growth of these cells was partially arrested at G1. In two of the three ini1-deficient cell lines, apoptosis was found to occur after the infection, as detected by the presence of cleaved poly (ADP-ribose) polymerase. To determine functional domains of INI1, we constructed plasmids expressing INI1 and its deletion mutants, which were used for a colony formation assay. Repeats 1 and 2 of INI1 were found to be required to suppress the growth of the three ini1-deficient cell lines. The results support the hypothesis that ini1 is a tumor suppressor gene and suggest a novel link between human SWI/SNF chromatin remodeling complex and apoptosis.

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Abbreviations

MRT:

malignant rhabdoid tumor

PARP:

poly (ADP-ribose) polymerase

MOI:

multiplicity of infection

CPE:

cytopathic effect

References

  • Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B . 1999 Cancer Res. 59: 74–79

  • Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R . 2000 Cell 102: 257–265

  • Brand A, Covert A . 2001 Gynecol. Oncol. 80: 99–103

  • Brodie SG, Deng CX . 2001 Trends Genet. 17: S18–S22

  • Cheng SW, Davies KP, Yung E, Beltran RJ, Yu J, Kalpana GV . 1999 Nat. Genet. 22: 102–105

  • Duriez PJ, Shah GM . 1997 Biochem. Cell. Biol. 75: 337–349

  • Garvin AJ, Re GG, Tarnowski BI, Hazen-Martin DJ, Sens DA . 1993 Am. J. Pathol. 142: 375–380

  • Graham FL, Smiley J, Russell WC, Nairn R . 1977 J. Gen. Virol. 36: 59–74

  • Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR . 1989 Gene 77: 61–68

  • Kalpana GV, Marmon S, Wang W, Crabtree GR, Goff SP . 1994 Science 266: 2002–2006

  • Kitamura Y, Ishikawa T, Okui N, Kobayashi N, Kanda T, Shimada T, Miyake K, Yoshiike K . 1999 J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 20: 105–114

  • Klochendler-Yeivin A, Fiette L, Barra J, Muchardt C, Babinet C, Yaniv M . 2000 EMBO Rep. 1: 500–506

  • Lee D, Sohn H, Kalpana GV, Choe J . 1999 Nature 399: 487–491

  • Muchardt C, Reyes JC, Bourachot B, Leguoy E, Yaniv M . 1996 EMBO J. 15: 3394–3402

  • Muchardt C, Sardet C, Bourachot B, Onufryk C, Yaniv M . 1995 Nucl. Acids Res. 23: 1127–1132

  • Murphy DJ, Hardy S, Engel DA . 1999 Mol. Cell. Biol. 19: 2724–2733

  • Okui N, Kobayashi N, Kitamura Y . 1998 J. Virol. 72: 6960–6964

  • Ota S, Crabbe DC, Tran TN, Triche TJ, Shimada H . 1993 Cancer 71: 2862–2872

  • Peebles PT, Trisch T, Papageorge AG . 1978 Pediat. Res. 12: 485–

  • Phelan ML, Sif S, Narlikar GJ, Kingston RE . 1999 Mol. Cell. 3: 247–253

  • Roberts CW, Galusha SA, McMenamin ME, Fletcher CD, Orkin SH . 2000 Proc. Natl. Acad. Sci. USA 97: 13796–13800

  • Rozenblatt-Rosen O, Rozovskaia T, Burakov D, Sedkov Y, Tillib S, Blechman J, Nakamura T, Croce CM, Mazo A, Canaani E . 1998 Proc. Natl. Acad. Sci. USA 95: 4152–4157

  • Scherer WF, Syverton JT, Gey GO . 1953 J. Exp. Med. 97: 695–

  • Sekiguchi M, Shiroko Y, Suzuki T, Imada M, Miyahara M, Fujii G . 1985 Biomed. Pharmacother. 39: 372–380

  • Sevenet N, Sheridan E, Amram D, Schneider P, Handgretinger R, Delattre O . 1999 Am. J. Hum. Genet. 65: 1342–1348

  • Sudarsanam P, Cao Y, Wu L, Laurent BC, Winston F . 1999 EMBO J. 18: 3101–3106

  • Sudarsanam P, Winston F . 2000 Trends Genet. 16: 345–351

  • Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O . 1998 Nature 394: 203–206

  • Wang W, Cote J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR . 1996 EMBO J. 15: 5370–5382

  • Whitehouse I, Flaus A, Havas K, Owen-Hughes T . 2000 Biochem. Soc. Trans. 28: 376–379

  • Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland AM, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH, Lees E . 2000 Cancer Res. 60: 6171–6177

  • Wu DY, Krumm A, Schubach WH . 2000 J. Virol. 74: 8893–8903

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Acknowledgements

We thank Yasuhide Hayashi (Department of Pediatrics, University of Tokyo) for KYM-1 and TM87-16 cells. We are grateful to Tadahito Kanda, Aikichi Iwamoto, Tetsuya Nakamura, Takashi Odawara (DID, IMS UT), Kunito Yoshiike (National Institute of Health, Thailand), and Hiroshi Yoshikura (NIID) for critical reading of the manuscript. This work was supported by grants to Y Kitamura from the Ministry of Health, Labour and Welfare; the Japan Human Sciences Foundation; and the Ministry of Education, Culture, Sports, Science and Technology Agency. K Ae is a recipient of a Resident Fellowship from the Japanese Foundation for AIDS Prevention.

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Authors and Affiliations

  1. Division of Molecular Genetics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan

    Keisuke Ae, Noriko Kobayashi, Ryuta Sakuma, Toshihiko Ogata & Yoshihiro Kitamura

  2. Division of Infectious Disease, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo, 103-8639, Japan

    Keisuke Ae, Noriko Kobayashi, Ryuta Sakuma & Yoshihiro Kitamura

  3. Section of Orthopedic Spinal Surgery Department of Frontier Surgical Therapeutics Division of Advanced Therapeutical Sciences Graduate School Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8519, Japan

    Keisuke Ae, Hiroshi Kuroda & Kenichi Shinomiya

  4. Department of Orthopedic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo, 170-0012, Japan

    Noriyoshi Kawaguchi

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  1. Keisuke Ae
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Correspondence to Yoshihiro Kitamura.

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Ae, K., Kobayashi, N., Sakuma, R. et al. Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells. Oncogene 21, 3112–3120 (2002). https://doi.org/10.1038/sj.onc.1205414

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