Transcription factor TFII-I causes transcriptional upregulation of GRP78 synthesis in prostate cancer cells.

Abstract

Receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) bind to cell surface-associated GRP78 and induce proliferative and survival signaling in prostate cancer cells. As part of the cellular response to alpha(2)M*, GRP78 expression is itself upregulated. In response to other stimuli, the transcription factor TFII-I upregulates GRP78 by binding to its gene promoter. We have, therefore, studied the role of TFII-I in transcriptional upregulation of GRP78 in 1-LN human prostate cancer cells stimulated with alpha(2)M*. This treatment caused a two- to threefold increase in TFII-I and GRP78 synthesis from [(35)S]-labeled precursor amino acids. Synthesis of both TFII-I and GRP78 were significantly reduced by silencing TFII-I gene expression or pretreatment of cells with genistein or actinomycin D. Confocal microscopy was employed to demonstrate relocation of TFII-I to the nucleus. In alpha(2)M*-stimulated cells, moreover, TFII-I bound to the GRP78 promoter as determined by CHIP assay. We also demonstrate binding of TFII-I to the c-fos promoter, consistent with its role in upregulating c-fos gene expression. In non-lymphoid cells, phosphorylated c-Src is an activator of TFII-I. Ligation of GRP78 on 1-LN cells with alpha(2)M* was followed by tyrosine phosphorylation of c-Src as well as TFII-I. We conclude that alpha(2)M*-induced increase in GRP78 synthesis is caused by transcriptional upregulation of TFII-I which binds to the GRP78 promoter and thus potentiates its cell survival and antipoptotic functions in 1-LN prostate cancer cells.

• Authors: U K Misra, F Wang, S V Pizzo
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 106 Issue 3 Pg. 381-9 (Feb 15 2009) ISSN: 1097-4644 [Electronic] United States
• PMID: 19097122 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• GTF2I protein, human
• HSPA5 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-fos
• Transcription Factors, TFII
• alpha-Macroglobulins
• Phosphotyrosine
• Protein-Tyrosine Kinases
• CSK Tyrosine-Protein Kinase
• src-Family Kinases
• CSK protein, human

Topics

• CSK Tyrosine-Protein Kinase
• Cell Line, Tumor
• Endoplasmic Reticulum Chaperone BiP
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Heat-Shock Proteins (biosynthesis, genetics)
• Humans
• Male
• Molecular Chaperones (biosynthesis, genetics)
• Phosphorylation
• Phosphotyrosine (metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Protein Binding
• Protein Transport
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-fos (metabolism)
• RNA Interference
• Transcription Factors, TFII (genetics, metabolism)
• Transcription, Genetic (drug effects, genetics)
• Up-Regulation (drug effects, genetics)
• alpha-Macroglobulins (pharmacology)
• src-Family Kinases