The purpose of this project is to investigate molecular mechanisms involved in the response of cells to hyperthermia. We will concentrate on determining the effect of clinically relevant hyperthermia doses an the functions of membrane enzyme systems involved in transmembrane signaling. Our preliminary data indicates that hyperthermia produces rapid and profound stimulation of the 3 major such systems. These are the adenylate cyclase, phospholipase C and phospholipase A2 systems. As these signaling systems are intimately involved in regulating all of the major functions of cells (proliferation, differentiation, metabolism, etc.) Their stimulation by hyperthermia may be highly significant. We will investigate the hypothesis that activation of transmembrane signal pathways generates cascade responses at the plasma membrane. These cascade responses may then be involved in mediating thermal cell killing, inducing thermotolerance and modulating tumor blood flow and cellular radiosensitivity. We will additionally examine the hypothesis that a common component of all signal transduction systems, the guanine nucleotide binding protein, constitutes a universal target for hyperthermia.
We aim to test the possibility that these proteins may serve as transducers of the physical effects of hyperthermia just as they transduce the chemical messages of hormones and other signalling agonists.
| Murshid, Ayesha; Prince, Thomas L; Lang, Ben et al. (2018) Role of Heat Shock Factors in Stress-Induced Transcription. Methods Mol Biol 1709:23-34 |
| Murshid, Ayesha; Theriault, Jimmy; Gong, Jianlin et al. (2018) Molecular Chaperone Receptors. Methods Mol Biol 1709:331-344 |
| Eguchi, Takanori; Calderwood, Stuart K; Takigawa, Masaharu et al. (2017) Intracellular MMP3 Promotes HSP Gene Expression in Collaboration With Chromobox Proteins. J Cell Biochem 118:43-51 |
| Calderwood, Stuart K; Gong, Jianlin (2016) Heat Shock Proteins Promote Cancer: It's a Protection Racket. Trends Biochem Sci 41:311-323 |
| Calderwood, Stuart K; Neckers, Len (2016) Hsp90 in Cancer: Transcriptional Roles in the Nucleus. Adv Cancer Res 129:89-106 |
| Eguchi, Taka; Prince, Thomas; Wegiel, Barbara et al. (2015) Role and Regulation of Myeloid Zinc Finger Protein 1 in Cancer. J Cell Biochem 116:2146-54 |
| Bunch, Heeyoun; Calderwood, Stuart K (2015) TRIM28 as a novel transcriptional elongation factor. BMC Mol Biol 16:14 |
| Calderwood, Stuart K (2015) Cdc37 as a co-chaperone to Hsp90. Subcell Biochem 78:103-12 |
| Murshid, Ayesha; Borges, Thiago J; Calderwood, Stuart K (2015) Emerging roles for scavenger receptor SREC-I in immunity. Cytokine 75:256-60 |
| Chou, Shiuh-Dih; Murshid, Ayesha; Eguchi, Takanori et al. (2015) HSF1 regulation of ?-catenin in mammary cancer cells through control of HuR/elavL1 expression. Oncogene 34:2178-2188 |
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