HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beresford, P. J. Articles by Lieberman, J. Search for Related Content PubMed PubMed Citation Articles by Beresford, P. J. Articles by Lieberman, J.

A Role for Heat Shock Protein 27 in CTL-Mediated Cell Death¹

The Center for Blood Research, Harvard Medical School, Boston, MA 02115

CTL exocytosis of granules containing perforin and granzyme proteases induces apoptotic cell death. Either granzyme A or B can act with perforin to trigger apoptosis. Granzyme B activates a ubiquitous apoptotic cascade induced by caspase cleavage, but the granzyme A pathway is largely unknown. Using affinity chromatography with recombinant mutant inactive granzyme A, we previously isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein) I and II. PHAP II, a substrate of granzyme A, is degraded within minutes of CTL attack. Two additional cytoplasmic proteins of 27 and 53 kDa bind strongly to the mutant granzyme A column, requiring 6 M urea to elute. Sequencing identified these as the monomer and dimer of hsp27, a small heat shock protein up-regulated by stress and cellular activation. Hsp27 coprecipitates with granzyme A from cytoplasmic lysates and is not a substrate of the enzyme. Hsp27 translocates to the detergent-insoluble fraction of target cells and relocalizes from diffuse cytoplasmic staining to long filamentous fibers, especially concentrated in a perinuclear region, within minutes of CTL attack. Hsp27 may participate in morphologic changes during granule-mediated lysis. Low or absent levels of hsp27 expression in T lymphocytes, even after heat shock, may play a role in CTL resistance to granule-mediated lysis.

This article has been cited by other articles:

				E. Schmitt, M. Gehrmann, M. Brunet, G. Multhoff, and C. Garrido Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy J. Leukoc. Biol., January 1, 2007; 81(1): 15 - 27. [Abstract] [Full Text] [PDF]

				A. J. Bredemeyer, P. E. Carrigan, T. A. Fehniger, D. F. Smith, and T. J. Ley Hop Cleavage and Function in Granzyme B-induced Apoptosis J. Biol. Chem., December 1, 2006; 281(48): 37130 - 37141. [Abstract] [Full Text] [PDF]

				R. Dressel, C. Grzeszik, M. Kreiss, D. Lindemann, T. Herrmann, L. Walter, and E. Gunther Differential Effect of Acute and Permanent Heat Shock Protein 70 Overexpression in Tumor Cells on Lysability by Cytotoxic T Lymphocytes Cancer Res., December 1, 2003; 63(23): 8212 - 8220. [Abstract] [Full Text] [PDF]

				C. Gross, W. Koelch, A. DeMaio, N. Arispe, and G. Multhoff Cell Surface-bound Heat Shock Protein 70 (Hsp70) Mediates Perforin-independent Apoptosis by Specific Binding and Uptake of Granzyme B J. Biol. Chem., October 17, 2003; 278(42): 41173 - 41181. [Abstract] [Full Text] [PDF]

				A. Wyttenbach, O. Sauvageot, J. Carmichael, C. Diaz-Latoud, A.-P. Arrigo, and D. C. Rubinsztein Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin Hum. Mol. Genet., May 1, 2002; 11(9): 1137 - 1151. [Abstract] [Full Text] [PDF]

				C. Paul, F. Manero, S. Gonin, C. Kretz-Remy, S. Virot, and A.-P. Arrigo Hsp27 as a Negative Regulator of Cytochrome c Release Mol. Cell. Biol., February 1, 2002; 22(3): 816 - 834. [Abstract] [Full Text] [PDF]

				P. J. Beresford, D. Zhang, D. Y. Oh, Z. Fan, E. L. Greer, M. L. Russo, M. Jaju, and J. Lieberman Granzyme A Activates an Endoplasmic Reticulum-associated Caspase-independent Nuclease to Induce Single-stranded DNA Nicks J. Biol. Chem., November 9, 2001; 276(46): 43285 - 43293. [Abstract] [Full Text] [PDF]

				P. Gain, G. Thuret, C. Chiquet, J. M. Dumollard, J. F. Mosnier, and L. Campos In situ immunohistochemical study of Bcl-2 and heat shock proteins in human corneal endothelial cells during corneal storage Br. J. Ophthalmol., August 1, 2001; 85(8): 996 - 1000. [Abstract] [Full Text] [PDF]

				A. K. De, K. M. Kodys, B. S. Yeh, and C. Miller-Graziano Exaggerated Human Monocyte IL-10 Concomitant to Minimal TNF-{alpha} Induction by Heat-Shock Protein 27 (Hsp27) Suggests Hsp27 Is Primarily an Antiinflammatory Stimulus J. Immunol., October 1, 2000; 165(7): 3951 - 3958. [Abstract] [Full Text] [PDF]

				R. Dressel, L. Elsner, T. Quentin, L. Walter, and E. Gunther Heat Shock Protein 70 Is Able to Prevent Heat Shock-Induced Resistance of Target Cells to CTL J. Immunol., March 1, 2000; 164(5): 2362 - 2371. [Abstract] [Full Text] [PDF]

				K. Guzik, J. Dobrucki, and J. Pryjma Heat-Shocked Monocytes Are Resistant to Staphylococcus aureus-Induced Apoptotic DNA Fragmentation due to Expression of HSP72 Infect. Immun., August 1, 1999; 67(8): 4216 - 4222. [Abstract] [Full Text] [PDF]

				E. R. Podack How to induce involuntary suicide: The need for dipeptidyl peptidase I PNAS, July 20, 1999; 96(15): 8312 - 8314. [Full Text] [PDF]

				H. Lambert, S. J. Charette, A. F. Bernier, A. Guimond, and J. Landry HSP27 Multimerization Mediated by Phosphorylation-sensitive Intermolecular Interactions at the Amino Terminus J. Biol. Chem., April 2, 1999; 274(14): 9378 - 9385. [Abstract] [Full Text] [PDF]