|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 12, 10489-10497, March 22, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Clinical Endocrinology Branch, NIDDK, National
Institutes of Health, Bethesda, Maryland 20892
Insulin-like growth factor (IGF)-binding
protein-3 (IGFBP-3) can stimulate apoptosis and inhibit cell
proliferation directly and independently of binding IGFs or indirectly
by forming complexes with IGF-I and IGF-II that prevent them from
activating the IGF-I receptor to stimulate cell survival and
proliferation. To date, IGF-independent actions only have been
demonstrated in a limited number of cells that do not synthesize or
respond to IGFs. To assess the general importance of IGF-independent
mechanisms, we have generated human IGFBP-3 mutants that cannot
bind IGF-I or IGF-II by substituting alanine for six residues in the
proposed IGF binding site,
Ile56/Tyr57/Arg75/Leu77/Leu80/Leu81,
and expressing the 6m-hIGFBP-3 mutant construct in Chinese hamster ovary cells. Binding of both IGF-I and IGF-II to 6m-hIGFBP-3 was reduced >80-fold. The nonbinding 6m-hIGFBP-3 mutant still was able to
inhibit DNA synthesis in a mink lung epithelial cell line in which
inhibition by wild-type hIGFBP-3 previously had been shown to be
exclusively IGF-independent. 6m-hIGFBP-3 only can act by
IGF-independent mechanisms since it is unable to form complexes with
the IGFs that inhibit their action. We next compared the ability of
wild-type and 6m-hIGFBP-3 to stimulate apoptosis in serum-deprived PC-3
human prostate cancer cells. PC-3 cells are known to synthesize and
respond to IGF-II, so that IGFBP-3 could potentially act by
either IGF-dependent or IGF-independent mechanisms. In
fact, 6m-hIGFBP-3 stimulated PC-3 cell death and stimulated apoptosis-induced DNA fragmentation to the same extent and with the
same concentration dependence as wild-type hIGFBP-3. These results
indicate that IGF-independent mechanisms are major contributors to
IGFBP-3-induced apoptosis in PC-3 cells and may play a wider role in
the antiproliferative and antitumorigenic actions of
IGFBP-3.
Insulin-like Growth Factor (IGF)-binding Protein-3 Mutants
That Do Not Bind IGF-I or IGF-II Stimulate Apoptosis in Human Prostate
Cancer Cells*
,
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Lexicon Genetics, 4000 Research Forest Dr., The
Woodlands, TX 77381.
§
To whom correspondence should be addressed: Bldg. 10, Rm. 8D12,
Clinical Endocrinology Branch, NIDDK, National Institutes of Health,
Bethesda, MD 20892. Tel.: 301-594-6796; Fax: 301-480-0262; E-mail,
mrechler@helix.nih.gov.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. RESSLER, J. RADHI, T. AIGNER, C. LOO, W. ZWERSCHKE, and C. SERGI Insulin-like Growth Factor-binding Protein-3 in Osteosarcomas and Normal Bone Tissues Anticancer Res, July 1, 2009; 29(7): 2579 - 2587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Yamada and K.-W. Lee Perspectives in mammalian IGFBP-3 biology: local vs. systemic action Am J Physiol Cell Physiol, May 1, 2009; 296(5): C954 - C976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Muhlbradt, E. Asatiani, E. Ortner, A. Wang, and E. P. Gelmann NKX3.1 Activates Expression of Insulin-like Growth Factor Binding Protein-3 to Mediate Insulin-like Growth Factor-I Signaling and Cell Proliferation Cancer Res., March 15, 2009; 69(6): 2615 - 2622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zappala, C. Elbi, J. Edwards, J. Gorenstein, M. M. Rechler, and N. Bhattacharyya Induction of Apoptosis in Human Prostate Cancer Cells by Insulin-Like Growth Factor Binding Protein-3 Does Not Require Binding to Retinoid X Receptor-{alpha} Endocrinology, April 1, 2008; 149(4): 1802 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Santer, B. Moser, G. A. Spoden, P. Jansen-Durr, and W. Zwerschke Human papillomavirus type 16 E7 oncoprotein inhibits apoptosis mediated by nuclear insulin-like growth factor-binding protein-3 by enhancing its ubiquitin/proteasome-dependent degradation Carcinogenesis, December 1, 2007; 28(12): 2511 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fu, J. A. Thompson, and L. A. Bach Promotion of Cancer Cell Migration: AN INSULIN-LIKE GROWTH FACTOR (IGF)-INDEPENDENT ACTION OF IGF-BINDING PROTEIN-6 J. Biol. Chem., August 3, 2007; 282(31): 22298 - 22306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, B. B. Madison, W. Zacharias, A. Kolterud, D. States, and D. L. Gumucio Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk Physiol Genomics, May 11, 2007; 29(3): 290 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yan, R. C. Baxter, B. Perbal, and S. M. Firth The Aminoterminal Insulin-Like Growth Factor (IGF) Binding Domain of IGF Binding Protein-3 Cannot Be Functionally Substituted by the Structurally Homologous Domain of CCN3 Endocrinology, November 1, 2006; 147(11): 5268 - 5274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Peng, P. J. Malloy, J. Wang, and D. Feldman Growth Inhibitory Concentrations of Androgens Up-Regulate Insulin-Like Growth Factor Binding Protein-3 Expression via an Androgen Response Element in LNCaP Human Prostate Cancer Cells Endocrinology, October 1, 2006; 147(10): 4599 - 4607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bhattacharyya, K. Pechhold, H. Shahjee, G. Zappala, C. Elbi, B. Raaka, M. Wiench, J. Hong, and M. M. Rechler Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus J. Biol. Chem., August 25, 2006; 281(34): 24588 - 24601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Severi, H. A. Morris, R. J. MacInnis, D. R. English, W. D. Tilley, J. L. Hopper, P. Boyle, and G. G. Giles Circulating insulin-like growth factor-I and binding protein-3 and risk of prostate cancer. Cancer Epidemiol. Biomarkers Prev., June 1, 2006; 15(6): 1137 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Peters, I. Tossidou, J. Achenbach, R. Woroniecki, M. Mengel, J.-K. Park, M. Paschy, K. de Groot, H. Haller, and M. Schiffer IGF-Binding Protein-3 Modulates TGF-beta/BMP-Signaling in Glomerular Podocytes J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1644 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cohen Insulin-like growth factor binding protein-3: insulin-like growth factor independence comes of age. Endocrinology, May 1, 2006; 147(5): 2109 - 2111. [Full Text] [PDF]
|
|
|
|
 |
|
 A M M Haydon, R J MacInnis, D R English, H Morris, and G G Giles Physical activity, insulin-like growth factor 1, insulin-like growth factor binding protein 3, and survival from colorectal cancer Gut, May 1, 2006; 55(5): 689 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Silha, P. C. Sheppard, S. Mishra, Y. Gui, J. Schwartz, J. G. Dodd, and L. J. Murphy Insulin-Like Growth Factor (IGF) Binding Protein-3 Attenuates Prostate Tumor Growth by IGF-Dependent and IGF-Independent Mechanisms Endocrinology, May 1, 2006; 147(5): 2112 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Santer, N. Bacher, B. Moser, D. Morandell, S. Ressler, S. M. Firth, G. A. Spoden, C. Sergi, R. C. Baxter, P. Jansen-Durr, et al. Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysis. Cancer Res., March 15, 2006; 66(6): 3024 - 3033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kibbey, M. J. Jameson, E. M. Eaton, and S. A. Rosenzweig Insulin-Like Growth Factor Binding Protein-2: Contributions of the C-Terminal Domain to Insulin-Like Growth Factor-1 Binding Mol. Pharmacol., March 1, 2006; 69(3): 833 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Oh, W.-Y. Kim, J.-H. Kim, M. N. Younes, A. K. El-Naggar, J. N. Myers, M. Kies, P. Cohen, F. Khuri, W. K. Hong, et al. Identification of Insulin-Like Growth Factor Binding Protein-3 as a Farnesyl Transferase Inhibitor SCH66336-Induced Negative Regulator of Angiogenesis in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., January 15, 2006; 12(2): 653 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Silha, Y. Gui, S. Mishra, A. Leckstrom, P. Cohen, and L. J. Murphy Overexpression of Gly56/Gly80/Gly81-Mutant Insulin-Like Growth Factor-Binding Protein-3 in Transgenic Mice Endocrinology, March 1, 2005; 146(3): 1523 - 1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, J. Xiang, and C. Duan Insulin-like Growth Factor-binding Protein-3 Plays an Important Role in Regulating Pharyngeal Skeleton and Inner Ear Formation and Differentiation J. Biol. Chem., February 4, 2005; 280(5): 3613 - 3620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yan, B. E. Forbes, K. A. McNeil, R. C. Baxter, and S. M. Firth Role of N- and C-terminal Residues of Insulin-like Growth Factor (IGF)-binding Protein-3 in Regulating IGF Complex Formation and Receptor Activation J. Biol. Chem., December 17, 2004; 279(51): 53232 - 53240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]
|
|
|
|
|
|
Z. Ren, Q. Cai, X.-O. Shu, H. Cai, C. Li, H. Yu, Y.-T. Gao, and W. Zheng Genetic Polymorphisms in the IGFBP3 Gene: Association with Breast Cancer Risk and Blood IGFBP-3 Protein Levels among Chinese Women Cancer Epidemiol. Biomarkers Prev., August 1, 2004; 13(8): 1290 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Dake, M. Boes, L. A. Bach, and R. S. Bar Effect of an Insulin-Like Growth Factor Binding Protein Fusion Protein on Thymidine Incorporation in Neuroblastoma and Rhabdomyosarcoma Cell Lines Endocrinology, July 1, 2004; 145(7): 3369 - 3374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mishra and L. J. Murphy Tissue Transglutaminase Has Intrinsic Kinase Activity: IDENTIFICATION OF TRANSGLUTAMINASE 2 AS AN INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 KINASE J. Biol. Chem., June 4, 2004; 279(23): 23863 - 23868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Cobb, D. A. M. Salih, I. Gonzalez, G. Tripathi, E. J. Carter, F. Lovett, C. Holding, and J. M. Pell Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function J. Cell Sci., May 1, 2004; 117(9): 1737 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mishra, A. Raz, and L. J. Murphy Insulin-Like Growth Factor Binding Protein-3 Interacts with Autocrine Motility Factor/Phosphoglucose Isomerase (AMF/PGI) and Inhibits the AMF/PGI Function Cancer Res., April 1, 2004; 64(7): 2516 - 2522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Kim, A. R. Ingermann, J. Tsubaki, S. M. Twigg, G. E. Walker, and Y. Oh Insulin-Like Growth Factor-Binding Protein 3 Induces Caspase-Dependent Apoptosis through a Death Receptor-Mediated Pathway in MCF-7 Human Breast Cancer Cells Cancer Res., March 15, 2004; 64(6): 2229 - 2237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mishra and L. J. Murphy Phosphorylation of Insulin-Like Growth Factor (IGF) Binding Protein-3 by Breast Cancer Cell Membranes Enhances IGF-I Binding Endocrinology, September 1, 2003; 144(9): 4042 - 4050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Payet, X.-H. Wang, R. C. Baxter, and S. M. Firth Amino- and Carboxyl-Terminal Fragments of Insulin-Like Growth Factor (IGF) Binding Protein-3 Cooperate to Bind IGFs with High Affinity and Inhibit IGF Receptor Interactions Endocrinology, July 1, 2003; 144(7): 2797 - 2806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Longobardi, M. Torello, C. Buckway, L. O'Rear, W. A. Horton, V. Hwa, C. T. Roberts Jr., F. Chiarelli, R. G. Rosenfeld, and A. Spagnoli A Novel Insulin-Like Growth Factor (IGF)-Independent Role for IGF Binding Protein-3 in Mesenchymal Chondroprogenitor Cell Apoptosis Endocrinology, May 1, 2003; 144(5): 1695 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Firth and R. C. Baxter Cellular Actions of the Insulin-Like Growth Factor Binding Proteins Endocr. Rev., December 1, 2002; 23(6): 824 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Butt, K. A. Fraley, S. M. Firth, and R. C. Baxter IGF-Binding Protein-3-Induced Growth Inhibition and Apoptosis Do Not Require Cell Surface Binding and Nuclear Translocation in Human Breast Cancer Cells Endocrinology, July 1, 2002; 143(7): 2693 - 2699. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |