HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal transition

Yihao Li; Xianjiang Kang; Qiang Wang

doi:10.1016/j.jgg.2011.02.001

Volume 38 Issue 3

Mar. 2011

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2011 > 38(3): 111-116

PDF( 561 KB)

HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal transition

doi: 10.1016/j.jgg.2011.02.001

a
College of Life Sciences, Hebei University, Baoding 071002, China
b
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

More Information

Corresponding author: E-mail address: qiangwang@ioz.ac.cn (Qiang Wang)
Received Date: 2010-11-29
Accepted Date: 2011-01-17
Rev Recd Date: 2011-01-16

Available Online: 2011-03-16

Publish Date: 2011-03-20

Abstract

Abstract

Smad2 and Smad3, the intracellular mediators of transforming growth factor β (TGF-β) signaling, are directly phosphorylated by the activated type I receptor kinase, and then shuttle from the cytoplasm into the nucleus to regulate target gene expression. Here, we report that the 70-kDa heat-shock protein (HSP70) interacts with Smad2 and decreases TGF-β signal transduction. Ectopic expression of HSP70 prevents receptor-dependent phosphorylation and nuclear translocation of Smad2, and blocks TGF-β-induced epithelial-mesenchymal transition (EMT) in HaCat cells. Our findings reveal an essential role of HSP70 in TGF-β-induced epithelial-mesenchymal transition (EMT) by impeding Smad2 phosphorylation.
- TGF-β,
- HSP70,
- Smad2,
- EMT

FullText(HTML)

References(22)

References

[1]	Calderwood, S.K., Khaleque, M.A., Sawyer, D.B. et al. Heat shock proteins in cancer: chaperones of tumorigenesis Trends Biochem. Sci., 31 (2006),pp. 164-172
[2]	Chen, X., Weisberg, E., Fridmacher, V. et al. Smad4 and FAST-1 in the assembly of activin-responsive factor Nature, 389 (1997),pp. 85-89
[3]	Chen, Y.G., Wang, Q., Lin, S.L. et al. Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis Exp. Biol. Med. (Maywood), 231 (2006),pp. 534-544
[4]	Feng, X.H., Derynck, R. Specificity and versatility in TGF-beta signaling through Smads Annu. Rev. Cell Dev. Biol., 21 (2005),pp. 659-693
[5]	Gorelik, L., Flavell, R.A. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease Immunity, 12 (2000),pp. 171-181
[6]	Jung, J.H., Lee, J.O., Kim, J.H. et al. Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation J. Cell Physiol., 223 (2010),pp. 408-414
[7]	Krakowski, A.R., Laboureau, J., Mauviel, A. et al. Cytoplasmic SnoN in normal tissues and nonmalignant cells antagonizes TGF-beta signaling by sequestration of the Smad proteins Proc. Natl. Acad. Sci. USA, 102 (2005),pp. 12437-12442
[8]	Kunwar, P.S., Zimmerman, S., Bennett, J.T. et al. Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in nodal signaling and mesendoderm induction Development, 130 (2003),pp. 5589-5599
[9]	Li, Z., Srivastava, P. Heat-shock proteins Curr. Protoc. Immunol. (2004)
[10]	Massague, J., Seoane, J., Wotton, D. Smad transcription factors Genes Dev., 19 (2005),pp. 2783-2810
[11]	Meacham, G.C., Patterson, C., Zhang, W. et al. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation Nat. Cell Biol., 3 (2001),pp. 100-105
[12]	Neupert, W., Brunner, M. The protein import motor of mitochondria Nat. Rev. Mol. Cell Biol., 3 (2002),pp. 555-565
[13]	Nylandsted, J., Brand, K., Jaattela, M. Heat shock protein 70 is required for the survival of cancer cells Ann. N.Y. Acad. Sci., 926 (2000),pp. 122-125
[14]	Ranelletti, F.O., Ricci, R., Larocca, L.M. et al. Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors Int. J. Cancer, 50 (1992),pp. 486-492
[15]	Schmierer, B., Hill, C.S. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility Nat. Rev. Mol. Cell Biol., 8 (2007),pp. 970-982
[16]	Sherman, M., Multhoff, G. Heat shock proteins in cancer Ann. N.Y. Acad. Sci., 1113 (2007),pp. 192-201
[17]	Shi, Y., Massague, J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus Cell, 113 (2003),pp. 685-700
[18]	Takaku, K., Oshima, M., Miyoshi, H. et al. Cell, 92 (1998),pp. 645-656
[19]	Taylor, I.W., Wrana, J.L. SnapShot: the TGFbeta pathway interactome Cell, 133 (2008),p. 378
[20]	Thomas, D.A., Massague, J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance Cancer Cell, 8 (2005),pp. 369-380
[21]	Xu, L., Chen, Y.G., Massague, J. The nuclear import function of Smad2 is masked by SARA and unmasked by TGFbeta-dependent phosphorylation Nat. Cell Biol., 2 (2000),pp. 559-562
[22]	Yang, Y., Janich, S., Cohn, J.A. et al. The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment Proc. Natl. Acad. Sci. USA, 90 (1993),pp. 9480-9484