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Investigation of the Subcellular Distribution of the bcl-2 Oncoprotein: Residence in the Nuclear Envelope, Endoplasmic Reticulum, and Outer Mitochondrial Membranes¹

Oncogene and Tumor Suppression Gene Program, La Jolla Cancer Research Foundation, La Jolla, California 92037 [J. C. R.], and Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510 [W. F.]

⁴ To whom requests for reprints should be addressed, at Oncogene and Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, 10901 N. Torrey Pines Road, La Jolla, CA 92037.

A multidisciplinary approach was taken to investigate the intracellular locations of the 26-kDa integral membrane protein encoded by the bcl-2 gene. Subcellular fractionation analysis of a t( 14; 18)-containing lymphoma cell line revealed the presence of Bcl-2 protein in nuclear, heavy-membrane, and light-membrane fractions but not in cytosol. Sedimentation of heavy-membrane fractions in Nycodenz and Percoll continuous gradients demonstrated comigration of p26-Bcl-2 with mitochondrial but not other organelle-associated proteins. Fractionation of light-membrane fractions using discontinuous sucrose-gradients revealed association of Bcl-2 protein primarily with lighter-density microsomes (smooth endoplasmic reticulum) as opposed to heavy-density microsomes (rough endoplasmic reticulum). Immune microscopy studies using laser-scanning microscopy, pre- and postembedding electron microscopic methods, and six different anti-Bcl-2 antibodies demonstrated Bcl-2 immunoreactivity in the nuclear envelope and outer mitochondrial membrane in a patchy distribution. Furthermore, anti-Bcl-2 antibody immunoreactivity generally appeared to directly overlie the nuclear envelope in high magnification electron microscopic studies, reminiscent of nuclear pore complexes. Addition of in vitro translated p26-Bcl-2 to isolated translocation-competent mitochondria revealed transmembrane domain-dependent association of Bcl-2 protein with mitochondria but provided no evidence for import into a protease-resistant compartment, consistent with immunomicroscopic localization to the outer mitochondrial membrane. Taken together, the findings demonstrate that p26-Bcl-2 resides primarily in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membrane in a nonuniform distribution suggestive of participation in protein complexes perhaps involved in some aspect of transport.

¹ This work was supported by NIH Grant CA-47956, American Cancer Society Grant DHP-71185, and a Scholar Award to J. C. R. from the Leukemia Society of America.

² S. K. and S. T. contributed equally to the data presented.

³ Present address: Department of Pediatrics, Mie University School of Medicine, Mie, Japan.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/ 4/93. Accepted 7/28/93.

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				N. D. Marchenko, A. Zaika, and U. M. Moll Death Signal-induced Localization of p53 Protein to Mitochondria. A POTENTIAL ROLE IN APOPTOTIC SIGNALING J. Biol. Chem., May 19, 2000; 275(21): 16202 - 16212. [Abstract] [Full Text] [PDF]

				M. Haraguchi, S. Torii, S.-i. Matsuzawa, Z. Xie, S. Kitada, S. Krajewski, H. Yoshida, T. W. Mak, and J. C. Reed Apoptotic Protease Activating Factor 1 (Apaf-1)-Independent Cell Death Suppression by Bcl-2 J. Exp. Med., May 15, 2000; 191(10): 1709 - 1720. [Abstract] [Full Text] [PDF]

				A. Gross, K. Pilcher, E. Blachly-Dyson, E. Basso, J. Jockel, M. C. Bassik, S. J. Korsmeyer, and M. Forte Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL Mol. Cell. Biol., May 1, 2000; 20(9): 3125 - 3136. [Abstract] [Full Text]

				G. Hausmann, L. A. O'Reilly, R. van Driel, J. G. Beaumont, A. Strasser, J. M. Adams, and D. C.S. Huang Pro-Apoptotic Apoptosis Protease-Activating Factor 1 (Apaf-1) Has a Cytoplasmic Localization Distinct from Bcl-2 or Bcl-XL J. Cell Biol., May 1, 2000; 149(3): 623 - 634. [Abstract] [Full Text] [PDF]

				W.-Y. Chan, K.-K. Cheung, J. O. Schorge, L.-W. Huang, W. R. Welch, D. A. Bell, R. S. Berkowitz, and S. C. Mok Bcl-2 and p53 Protein Expression, Apoptosis, and p53 Mutation in Human Epithelial Ovarian Cancers Am. J. Pathol., February 1, 2000; 156(2): 409 - 417. [Abstract] [Full Text] [PDF]

				D. G. Nicholls and S. L. Budd Mitochondria and Neuronal Survival Physiol Rev, January 1, 2000; 80(1): 315 - 360. [Abstract] [Full Text] [PDF]

				B. O’Rourke Apoptosis : Rekindling the Mitochondrial Fire Circ. Res., November 12, 1999; 85(10): 880 - 883. [Full Text] [PDF]

				A. Alberici, D. Moratto, L. Benussi, L. Gasparini, R. Ghidoni, L. B. Gatta, D. Finazzi, G. B. Frisoni, M. Trabucchi, J. H. Growdon, et al. Presenilin 1 Protein Directly Interacts with Bcl-2 J. Biol. Chem., October 22, 1999; 274(43): 30764 - 30769. [Abstract] [Full Text] [PDF]

				B. FADEEL, B. ZHIVOTOVSKY, and S. ORRENIUS All along the watchtower: on the regulation of apoptosis regulators FASEB J, October 1, 1999; 13(13): 1647 - 1657. [Abstract] [Full Text]

				X.-H. Liu, J. C. Castelli, and R. J. Youle Receptor-mediated uptake of an extracellular Bcl-xL fusion protein inhibits apoptosis PNAS, August 17, 1999; 96(17): 9563 - 9567. [Abstract] [Full Text] [PDF]

				N. Cirelli, A. Moens, P. Lebrun, C. Gueuning, J. Delogne-Desnoeck, A.-M. Vanbellinghen, and S. Meuris Apoptosis in Human Term Placenta Is Not Increased during Labor but Can Be Massively Induced In Vitro Biol Reprod, August 1, 1999; 61(2): 458 - 463. [Abstract] [Full Text]

				A. Gross, J. M. McDonnell, and S. J. Korsmeyer BCL-2 family members and the mitochondria in apoptosis Genes & Dev., August 1, 1999; 13(15): 1899 - 1911. [Full Text]

				B. W. Johnson and L. H. Boise Bcl-2 and Caspase Inhibition Cooperate to Inhibit Tumor Necrosis Factor-alpha -induced Cell Death in a Bcl-2 Cleavage-independent Fashion J. Biol. Chem., June 25, 1999; 274(26): 18552 - 18558. [Abstract] [Full Text] [PDF]

				E. Bossy-Wetzel and D. R. Green Caspases Induce Cytochrome c Release from Mitochondria by Activating Cytosolic Factors J. Biol. Chem., June 18, 1999; 274(25): 17484 - 17490. [Abstract] [Full Text] [PDF]

				A. M. Dharmarajan, S. Hisheh, B. Singh, S. Parkinson, K. I. Tilly, and J. L. Tilly Antioxidants Mimic the Ability of Chorionic Gonadotropin to Suppress Apoptosis in the Rabbit Corpus Luteum in Vitro: A Novel Role for Superoxide Dismutase in Regulating bax Expression Endocrinology, June 1, 1999; 140(6): 2555 - 2561. [Abstract] [Full Text]

				A. Nishimura Changes in Bcl-2 and Bax Expression in Rat Tongue during 4-Nitroquinoline 1-oxide-induced Carcinogenesis Journal of Dental Research, June 1, 1999; 78(6): 1264 - 1269. [Abstract] [PDF]

				S. Krajewski, M. Krajewska, L. M. Ellerby, K. Welsh, Z. Xie, Q. L. Deveraux, G. S. Salvesen, D. E. Bredesen, R. E. Rosenthal, G. Fiskum, et al. Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia PNAS, May 11, 1999; 96(10): 5752 - 5757. [Abstract] [Full Text] [PDF]

				L. Jia, M. G. Macey, Y. Yin, A. C. Newland, and S. M. Kelsey Subcellular Distribution and Redistribution of Bcl-2 Family Proteins in Human Leukemia Cells Undergoing Apoptosis Blood, April 1, 1999; 93(7): 2353 - 2359. [Abstract] [Full Text] [PDF]

				M. Tamatani, Y. H. Che, H. Matsuzaki, S. Ogawa, H. Okado, S.-i. Miyake, T. Mizuno, and M. Tohyama Tumor Necrosis Factor Induces Bcl-2 and Bcl-x Expression through NFkappa B Activation in Primary Hippocampal Neurons J. Biol. Chem., March 26, 1999; 274(13): 8531 - 8538. [Abstract] [Full Text] [PDF]

				J. F. Krebs, R. C. Armstrong, A. Srinivasan, T. Aja, A. M. Wong, A. Aboy, R. Sayers, B. Pham, T. Vu, K. Hoang, et al. Activation of Membrane-associated Procaspase-3 Is Regulated by Bcl-2 J. Cell Biol., March 8, 1999; 144(5): 915 - 926. [Abstract] [Full Text] [PDF]

				C. V. Suschek, V. Krischel, D. Bruch-Gerharz, D. Berendji, J. Krutmann, K.-D. Kroncke, and V. Kolb-Bachofen Nitric Oxide Fully Protects against UVA-induced Apoptosis in Tight Correlation with Bcl-2 Up-regulation J. Biol. Chem., March 5, 1999; 274(10): 6130 - 6137. [Abstract] [Full Text] [PDF]

				B. A. Froesch, C. Aime-Sempe, B. Leber, D. Andrews, and J. C. Reed Inhibition of p53 Transcriptional Activity by Bcl-2 Requires Its Membrane-anchoring Domain J. Biol. Chem., March 5, 1999; 274(10): 6469 - 6475. [Abstract] [Full Text] [PDF]

				W.-X. Zong, L. C. Edelstein, C. Chen, J. Bash, and C. Gélinas The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappa B that blocks TNFalpha -induced apoptosis Genes & Dev., February 15, 1999; 13(4): 382 - 387. [Abstract] [Full Text]

				D. A. Jans, V. R. Sutton, P. Jans, C. J. Froelich, and J. A. Trapani BCL-2 Blocks Perforin-induced Nuclear Translocation of Granzymes Concomitant with Protection against the Nuclear Events of Apoptosis J. Biol. Chem., February 12, 1999; 274(7): 3953 - 3961. [Abstract] [Full Text] [PDF]

				P. B. Poommipanit, B. Chen, and Z. N. Oltvai Interleukin-3 Induces the Phosphorylation of a Distinct Fraction of Bcl-2 J. Biol. Chem., January 8, 1999; 274(2): 1033 - 1039. [Abstract] [Full Text] [PDF]

				G. MacDonald, L. Shi, C. V. Velde, J. Lieberman, and A. H. Greenberg Mitochondria-dependent and -independent Regulation of Granzyme B-induced Apoptosis J. Exp. Med., January 4, 1999; 189(1): 131 - 144. [Abstract] [Full Text] [PDF]

				M. S. Czuczman, A. J. Grillo-Lopez, C. A. White, M. Saleh, L. Gordon, A. F. LoBuglio, C. Jonas, D. Klippenstein, B. Dallaire, and C. Varns Treatment of Patients With Low-Grade B-Cell Lymphoma With the Combination of Chimeric Anti-CD20 Monoclonal Antibody and CHOP Chemotherapy J. Clin. Oncol., January 1, 1999; 17(1): 268 - 268. [Abstract] [Full Text] [PDF]

				S.J. KORSMEYER, A. GROSS, H. HARADA, J. ZHA, K. WANG, X.-M. YIN, M. WEI, and S. ZINKEL Death and Survival Signals Determine Active/Inactive Conformations of Pro-apoptotic BAX, BAD, and BID Molecules Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 343 - 350. [Abstract] [PDF]

				X. Deng, T. Ito, B. Carr, M. Mumby, and W. S. May Jr. Reversible Phosphorylation of Bcl2 following Interleukin 3 or Bryostatin 1 Is Mediated by Direct Interaction with Protein Phosphatase 2A J. Biol. Chem., December 18, 1998; 273(51): 34157 - 34163. [Abstract] [Full Text] [PDF]