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Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin.

Publication ,  Journal Article
Misra, UK; Mowery, YM; Gawdi, G; Pizzo, SV
Published in: J Cell Biochem
June 2011

Receptor-recognized forms of α₂ -macroglobulin (α₂ M) bind to cell surface-associated GRP78 and initiate pro-proliferative and anti-apoptotic signaling. Ligation of GRP78 with α₂ M also upregulates TFII-I, which binds to the GRP78 promoter and enhances GRP78 synthesis. In addition to its transcriptional functions, cytosolic TFII-I regulates agonist-induced Ca(2+) entry. In this study we show that down regulation of TFII-I gene expression by RNAi profoundly impairs its cell surface expression and anti-apoptotic signaling as measured by significant reduction of GRP78, Bcl-2, and cyclin D1 in 1-Ln and DU-145 human prostate cancer cells stimulated with α₂ M. In contrast, this treatment significantly increases levels of the pro-apoptotic proteins p53, p27, Bax, and Bak and causes DNA fragmentation. Furthermore, down regulation of TFII-I expression activates agonist-induced Ca(2+) entry. In plasma membrane lysates p-PLCγ1, TRPC3, GRP78, MTJ1, and caveolin co-immunoprecipitate with TFII-I suggesting multimeric complexes of these proteins. Consistent with this hypothesis, down regulating TFII-I, MTJ1, or GRP78 expression by RNAi greatly attenuates cell surface expression of TFII-I. In conclusion, we demonstrate that not only does cell surface GRP78 regulate apoptosis, but it also regulates Ca(2+) homeostasis by controlling cell surface localization of TFII-I.

Duke Scholars

Published In

J Cell Biochem

DOI

EISSN

1097-4644

Publication Date

June 2011

Volume

112

Issue

6

Start / End Page

1685 / 1695

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Transcription Factors, TFII
  • TRPC Cation Channels
  • RNA Interference
  • Protein Binding
  • Prostatic Neoplasms
  • Membrane Proteins
  • Male
  • Immunoprecipitation
  • Humans
 

Citation

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ICMJE
MLA
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Misra, U. K., Mowery, Y. M., Gawdi, G., & Pizzo, S. V. (2011). Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin. J Cell Biochem, 112(6), 1685–1695. https://doi.org/10.1002/jcb.23083
Misra, U. K., Y. M. Mowery, G. Gawdi, and S. V. Pizzo. “Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin.J Cell Biochem 112, no. 6 (June 2011): 1685–95. https://doi.org/10.1002/jcb.23083.
Misra UK, Mowery YM, Gawdi G, Pizzo SV. Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin. J Cell Biochem. 2011 Jun;112(6):1685–95.
Misra, U. K., et al. “Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin.J Cell Biochem, vol. 112, no. 6, June 2011, pp. 1685–95. Pubmed, doi:10.1002/jcb.23083.
Misra UK, Mowery YM, Gawdi G, Pizzo SV. Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α₂ -macroglobulin. J Cell Biochem. 2011 Jun;112(6):1685–1695.
Journal cover image

Published In

J Cell Biochem

DOI

EISSN

1097-4644

Publication Date

June 2011

Volume

112

Issue

6

Start / End Page

1685 / 1695

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Transcription Factors, TFII
  • TRPC Cation Channels
  • RNA Interference
  • Protein Binding
  • Prostatic Neoplasms
  • Membrane Proteins
  • Male
  • Immunoprecipitation
  • Humans