HSPA1A is an important regulator of the stability and function of ZNF198 and its oncogenic derivative, ZNF198-FGFR1

Chitta S. Kasyapa, Padmaja Kunapuli, John Kenneth Cowell

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mass spectroscopy analysis demonstrated that the HSPA1A protein is found in complex with the ZNF198 protein which is involved in a chromosome rearrangement with the FGFR1 gene in an atypical myeloproliferative disease. HSPA1A is a member of the HSP70 family of genes which has been shown to be inducible in a variety of circumstances. Exogenous expression of the ZNF198-FGFR1 fusion kinase gene as well as ZNF198 in a model cell system results in a large (>650-fold) increase in HSP70 mRNA levels. Using KNK437, a specific inhibitor of HSP70 transcription, we have demonstrated that an important function of HSPA1A is to stabilize the ZNF198 and ZNF198-FGFR1 proteins. In the absence of HSPA1 A, specific functions of ZNF198-FGFR1 such as STAT3 phosphorylation is also lost. Treatment of cells with KNK437 in the presence of MG132, an inhibitor of proteasomal degradation of proteins, suggested that only the ZNF198-FGFR1 protein is subject to the proteasomal degradation pathway, while ZNF198 is not. These observations suggest an important role for HSPA1A in ZNF198 and ZNF198-FGFR1 mediated cellular function.

Original languageEnglish (US)
Pages (from-to)1308-1317
Number of pages10
JournalJournal of Cellular Biochemistry
Volume102
Issue number5
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

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Receptor, Fibroblast Growth Factor, Type 1
Genes
Derivatives
Gene Fusion
Proteolysis
Degradation
Mass Spectrometry
Phosphorylation
Proteins
Phosphotransferases
Chromosomes
Corrosion inhibitors
Transcription
Messenger RNA
Fusion reactions
Cells
Spectroscopy
KNK 437

Keywords

  • HSPA1A
  • KNK437
  • Myeloproliferative disease
  • ZNF198-FGFR1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

HSPA1A is an important regulator of the stability and function of ZNF198 and its oncogenic derivative, ZNF198-FGFR1. / Kasyapa, Chitta S.; Kunapuli, Padmaja; Cowell, John Kenneth.

In: Journal of Cellular Biochemistry, Vol. 102, No. 5, 01.12.2007, p. 1308-1317.

Research output: Contribution to journalArticle

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