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 language | English (US) |
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Pages (from-to) | 1308-1317 |
Number of pages | 10 |
Journal | Journal of cellular biochemistry |
Volume | 102 |
Issue number | 5 |
DOIs | |
State | Published - Dec 1 2007 |
Externally published | Yes |
Keywords
- HSPA1A
- KNK437
- Myeloproliferative disease
- ZNF198-FGFR1
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology