MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer
1
Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue/CLS 610, Boston, MA 02115, USA
2
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
3
Departments of Urology and Functional Genomics, Geisinger Clinic, Danville, PA 17822, USA
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(6), 792; https://doi.org/10.3390/cancers11060792
Received: 4 May 2019
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Revised: 1 June 2019
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Accepted: 5 June 2019
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Published: 8 June 2019
(This article belongs to the Special Issue Molecular Stress Response Dysregulation in Cancer: Therapeutic Targets and Opportunities)
Cell division control 37 (CDC37) increases the stability of heat shock protein 90 (HSP90) client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SREZBP-CTfin51-AW1-Number 18 cDNA (SCAN) transcription factor family—MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1/ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced the tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in the CDC37 gene, negatively regulated the CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.
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Keywords:
SCAN zinc finger; SCAND1; CDC37; MZF1; prostate cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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Doi: doi: 10.20944/preprints201905.0062.v1
Link: https://doi.org/10.1101/617753
MDPI and ACS Style
Eguchi, T.; Prince, T.L.; Tran, M.T.; Sogawa, C.; Lang, B.J.; Calderwood, S.K. MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer. Cancers 2019, 11, 792. https://doi.org/10.3390/cancers11060792
AMA Style
Eguchi T, Prince TL, Tran MT, Sogawa C, Lang BJ, Calderwood SK. MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer. Cancers. 2019; 11(6):792. https://doi.org/10.3390/cancers11060792
Chicago/Turabian StyleEguchi, Takanori, Thomas L. Prince, Manh T. Tran, Chiharu Sogawa, Benjamin J. Lang, and Stuart K. Calderwood. 2019. "MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer" Cancers 11, no. 6: 792. https://doi.org/10.3390/cancers11060792
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