ABSTRACT Overexpression of CD30 and constitutive nuclear factor-_κ_B (NF-_κ_B) activation are hallmarks of the malignant Hodgkin Reed–Sternberg (H-RS) cells. Previous investigations have

demonstrated that both proliferation and survival of H-RS cells require constitutive NF-_κ_B activity, which is comprised of the p50 and RelA subunits. We report here enhanced expression of

NF-_κ_B2/p52 and RelB-containing NF-_κ_B DNA-binding activity in Epstein–Barr virus-negative H-RS cells. Kinetic studies revealed that a proteasome inhibitor MG132 induced p100 accumulation

with reduced p52 expression in H-RS cells, suggesting proteasome-dependent processing of p100. In addition, treatment with a protein synthesis inhibitor cycloheximide rapidly downregulated

activation pathway, and suggest that deregulated CD30 signaling contributes to the neoplastic features of H-RS cells. Access through your institution Buy or subscribe This is a preview of

subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only

$5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout

ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS INABILITY TO PHOSPHORYLATE Y88

OF P27KIP1 ENFORCES REDUCED P27 PROTEIN LEVELS AND ACCELERATES LEUKEMIA PROGRESSION Article Open access 21 May 2022 PPM1D ACTIVITY PROMOTES CELLULAR TRANSFORMATION BY PREVENTING SENESCENCE

AND CELL DEATH Article Open access 05 September 2024 A NOVEL MODEL OF ALTERNATIVE NF-ΚB PATHWAY ACTIVATION IN ANAPLASTIC LARGE CELL LYMPHOMA Article 12 November 2020 ABBREVIATIONS * EBV:

Epstein–Barr virus * EMSA: electrophoretic mobility shift assay * HL: Hodgkin lymphoma * H-RS cells: Hodgkin/Reed–Sternberg cells * I_κ_B: inhibitor of NF-_κ_B * IKK: I_κ_B kinase * NF-_κ_B:

nuclear factor-_κ_B * NEMO: NF-_κ_B essential modulator * NIK: NF-_κ_B-inducing kinase * TNF: tumor necrosis factor * TNFR: TNF receptor * TRAF: TNF receptor-associated factor REFERENCES *

Annunziata CM, Safiran YJ, Irving SG, Kasid UN and Cossman J . (2000). _Blood_, 96, 2841–2848. * Atkinson PGP, Coope HJ, Rowe M and Ley SC . (2003). _J. Biol. Chem._, 278, 51134–51142. *

Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W, Royer HD, Grinstein E, Greiner A, Scheidereit C and Dörken B . (1997). _J. Clin. Invest._, 100, 2961–2969. * Barth TFE,

Martin-Subero JI, Joos S, Menz CK, Hasel C, Mechtersheimer G, Parwaresch RM, Lichter P, Siebert R and Möller P . (2003). _Blood_, 101, 3681–3686. * Ben-Neriah Y and Schmitz ML . (2004).

_EMBO Rep_, 5, 668–673. * Cabannes E, Khan G, Aillet F, Jarrett RF and Hay RT . (1999). _Oncogene_, 18, 3063–3070. * Carbone A, Gloghini A, Gattei V, Aldinucci D, Degan M, Paoli P, De

Zagonel V and Pinto A . (1995). _Blood_, 85, 780–789. * Chen LF and Greene WC . (2004). _Nat. Rev. Mol. Cell. Biol._, 5, 392–401. * Chinanonwait N, Miura H, Yamamoto N and Yamaoka S .

(2002). _FEBS Lett._, 531 (3), 553–560. * Claudio E, Brown K, Park S, Wang H and Siebenlist U . (2002). _Nat. Immunol._, 3, 958–965. * Cogswell PC, Guttridge DC, Funkhouser WK and Baldwin AS

. (2000). _Oncogene_, 19, 1123–1131. * Coope HJ, Atkinson PGP, Huhse B, Belich M, Janzen J, Holman MJ, Klaus GGB, Johnston LH and Ley SC . (2002). _EMBO J._, 21, 5375–5385. * Dejardin E,

Deregowski V, Chapelier M, Jacobs N, Gielen J, Merville MP and Bours V . (1999). _Oncogene_, 18, 2567–2577. * Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware

CF and Green DR . (2002). _Immunity_, 17, 525–535. * Derudder E, Dejardin E, Pritchard LL, Green DR, Körner M and Baud V . (2003). _J. Biol. Chem._, 278, 23278–23284. * Eliopoulos AG,

Caamano JH, Flavell J, Reynolds GM, Murray, PG, Poyet JL and Young LS . (2003). _Oncogene_, 22, 7557–7569. * Emmerich F, Theurich S, Hummel M, Haeffker A, Vry MS, Döhner K, Bommert K, Stein

H and Dörken B . (2003). _J. Pathol._, 201, 413–420. * Fiumara P, Snell V, Li Y, Mukhopadhyay A, Younes M, Gillenwater AM, Cabanillas F, Aggarwal BB and Younes A . (2001). _Blood_, 98,

2784–2790. * Hanada K, Tsunoda R and Hamada H . (1996). _J. Leukoc. Biol._, 60, 181–190. * Hinz M, Lemke P, Anagnostopoulos I, Hacker C, Krappmann D, Mathas S, Dörken B, Zenke M, Stein H and

Scheidereit C . (2002). _J. Exp. Med._, 196, 605–617. * Hironaka N, Mochida K, Mori N, Maeda M, Yamamoto N and Yamaoka S . (2004). _Neoplasia_, 6, 266–278. * Horie R, Higashihara M and

Watanabe T . (2003). _Int. J. Hematol._, 77, 37–47. * Horie R, Watanabe M, Ishida T, Koiwa T, Aizawa S, Itoh K, Higashihara M, Kadin ME and Watanabe T . (2004). _Cancer Cell_, 5, 353–364. *

Horie R, Watanabe T, Morishita Y, Ito K, Ishida T, Kanegae Y, Saito I, Higashihara M, Mori S, Kadin ME and Watanabe T . (2002). _Oncogene_, 21, 2493–2503. * Hsu H, Shu HB, Pan MG and Goeddel

DV . (1996). _Cell_, 84, 299–308. * Hübinger G, Schneider C, Stöhr D, Ruff H, Kirchner D, Schwänen C, Schmid M, Bergmann L and Müller E . (2004). _Exp. Hematol._, 32, 382–389. * Joos S,

Menz CK, Wrobel G, Siebert R, Gesk S, Ohl S, Mechtersheimer G, Trümper L, Möller P, Lichter P and Barth TFE . (2002). _Blood_, 99, 1381–1387. * Kawakami Y, Miura T, Bissonnette R, Hata D,

Khan WN, Kitamura T, Maeda-Yamamoto M, Hartman SE, Yao L, Alt FW and Kawakami T . (1997). _Proc. Natl. Acad. Sci. USA_, 94, 3938–3942. * Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W,

French DM, Grewal IS, Cochran AG, Gordon NC, Yin JP, Starovasnik MA and Dixit VM . (2002). _Immunity_, 17, 515–524. * Krappmann D, Emmerich F, Kordes U, Scharschmidt E, Dörken B and

Scheidereit C . (1999). _Oncogene_, 18, 943–953. * Küppers R, Klein U, Schwering I, Distler V, Bräninger A, Cattoretti G, Tu Y, Stolovitzky GA, Califano A, Hansmann M-L and Dalla-Favera R .

(2003). _J. Clin. Invest._, 111, 529–537. * Liao G, Zhang M, Harhaj EW and Sun SC . (2004). _J. Biol. Chem._, 279, 26243–26250. * Li Q and Verma ML . (2002). _Nat. Rev. Immunol._, 2,

725–734. * Makris C, Roberts JL and Karin M . (2002). _Mol. Cell. Biol._, 22, 6573–6581. * Martín-Subero JI, Gesk S, Harder L, Sonoki T, Tucker PW, Schlegelberger B, Grote W, Novo FJ,

Calasanz MJ, Hansmann ML, Dyer MJS and Siebert R . (2002). _Blood_, 99, 1474–1477. * Mathas S, Lietz A, Janz M, Hinz M, Jundt F, Scheidereit C, Bommert K and Dörken B . (2003). _Blood_, 102,

1028–1034. * Mori N, Fujii M, Iwai K, Ikeda S, Yamasaki Y, Hata T, Yamada Y, Tanaka Y, Tomonaga M and Yamamoto N . (2000). _Blood_, 95, 3915–3921. * Morita S, Kojima T and Kitamura T .

(2000). _Gene Ther._, 7, 1063–1066. * Müller JR and Siebenlist U . (2003). _J. Biol. Chem._, 278, 12006–12012. * Munoz E, Courtois G, Veschambre P, Jalinot P and Israël A . (1994). _J.

Virol._, 68, 8035–8044. * Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP and Teitelbaum SL . (2003). _J. Exp. Med._, 198, 771–781. * Opat S and Gaston JS . (2000).

_Autoimmunity_, 33, 45–60. * Saito N, Courtois G, Chiba A, Yamamoto N, Nitta T, Hironaka N, Rowe M, Yamamoto N and Yamaoka S . (2003). _J. Biol. Chem._, 278, 46565–46575. * Saitoh T,

Nakayama M, Nakano H, Yagita H, Yamamoto N and Yamaoka S . (2003). _J. Biol. Chem._, 278, 36005–36012. * Schneider C and Hübinger G . (2002). _Leuk. Lymphoma_, 43, 1355–1366. * Skinnider BF

and Mak TW . (2002). _Blood_, 99, 4283–4297. * Solan NJ, Miyoshi H, Carmona EM, Bren GD and Paya CV . (2002). _J. Biol. Chem._, 277, 1405–1418. * Stein H, Foss HD, Dürkop H, Marafioti T,

Delsol G, Pulford K, Pileri S and Falini B . (2000). _Blood_, 96, 3681–3695. * Sugamura K, Fujii M, Kannagi M, Sakitani M, Takeuchi M and Hinuma Y . (1984). _Int. J. Cancer._, 34, 221–228. *

Takahashi Y, Tanaka Y, Yamashita A, Koyanagi Y, Nakamura M and Yamamoto N . (2001). _J. Virol._, 75, 6748–6757. * Thomas RK, Re D, Wolf J and Diehl V . (2004). _Lancet Oncol._, 5, 11–18. *

Whiteside ST, Ernst MK, LeBail O, Laurent-Winter C, Rice N and Israël A . (1995). _Mol. Cell. Biol._, 15, 5339–5345. * Xiao G, Cvijic ME, Fong A, Harhaj EW, Uhlik MT, Waterfield M and Sun SC

. (2001). _EMBO J._, 20, 6805–6815. * Yamaoka S, Courtois G, Bessia C, Whiteside ST, Weil R, Agou F, Kirk HE, Kay RJ and Israël A . (1998). _Cell_, 93, 1231–1240. * Yamaoka S, Inoue H,

Sakurai M, Sugiyama T, Hazama M, Yamada T and Hatanaka M . (1996). _EMBO J._, 15, 873–887. * Zheng B, Fiumara P, Li YV, Georgakis G, Snell V, Younes M, Vauthey JN, Carbone A and Younes A .

(2003). _Blood_, 102, 1019–1027. Download references ACKNOWLEDGEMENTS We thank Drs N Rice and A Israël (Institut Pasteur de Paris) for plasmids and antisera, Dr D Goeddel (Amgen, CA) for NIK

plasmids and Dr T Kitamura (University of Tokyo) for the pMX vector and PLAT-E cells. We also thank the members of Department of Molecular Virology for helpful discussion. This work was

supported by Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology to NY and SY, grant from the Ministry of Health,

Labor and Welfare of Japan and the Human Science Foundation to NY, and Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology to SY.

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo, 113-8510, Japan

Mizuho Nonaka, Naoki Yamamoto & Shoji Yamaoka * Fourth Department of Internal Medicine, School of Medicine, Kitasato University, Kanagawa, Japan Ryouichi Horie * Second Department of

Pathology, School of Medicine, Toho University, Tokyo, Japan Kinji Itoh * Division of Pathology, Department of Cancer Research, The Institute of Medical Science, The University of Tokyo,

Tokyo, Japan Toshiki Watanabe Authors * Mizuho Nonaka View author publications You can also search for this author inPubMed Google Scholar * Ryouichi Horie View author publications You can

also search for this author inPubMed Google Scholar * Kinji Itoh View author publications You can also search for this author inPubMed Google Scholar * Toshiki Watanabe View author

publications You can also search for this author inPubMed Google Scholar * Naoki Yamamoto View author publications You can also search for this author inPubMed Google Scholar * Shoji Yamaoka

View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Shoji Yamaoka. RIGHTS AND PERMISSIONS Reprints and permissions

ABOUT THIS ARTICLE CITE THIS ARTICLE Nonaka, M., Horie, R., Itoh, K. _et al._ Aberrant NF-_κ_B2/p52 expression in Hodgkin/Reed–Sternberg cells and CD30-transformed rat fibroblasts.

_Oncogene_ 24, 3976–3986 (2005). https://doi.org/10.1038/sj.onc.1208564 Download citation * Received: 06 September 2004 * Revised: 24 January 2005 * Accepted: 24 January 2005 * Published: 14

March 2005 * Issue Date: 02 June 2005 * DOI: https://doi.org/10.1038/sj.onc.1208564 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS *

Hodgkin/Reed–Sternberg cells * CD30 * NF-_κ_B2 * IKK