The cyclin D1 proto-oncogene is sequestered in the cytoplasm of mammalian cancer cell lines

Molecular Cancer
John P AlaoDavid M Vigushin

Abstract

The cyclin D1 proto-oncogene is an important regulator of G1 to S-phase transition and an important cofactor for several transcription factors in numerous cell types. Studies on neonatal cardiomyocytes and postmitotic neurons indicate that the activity of cyclin D1 may be regulated through its cytoplasmic sequestration. We have demonstrated previously, that TSA induces the ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells. Additional studies were initiated in order to further investigate the effect of TSA on cyclin D1 regulation using sub-cellular fractionation techniques. Our studies revealed cyclin D1 to be localized predominantly within the cytoplasmic fraction of all cell lines tested. These observations were confirmed by confocal microscopy. GSK3beta was found to be localized within both the nucleus and cytoplasm throughout the cell cycle. Inhibition of GSK3beta or CRM1-dependent nuclear export resulted in only modest nuclear accumulation, suggesting that the cytoplasmic localization of cyclin D1 results from the inhibition of its nuclear import. We have shown by several different experimental approaches, that cyclin D1 is in fact a predominantly cytoplasmic protein in mammalian cancer cell lines. R...Continue Reading

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Citations

Dec 8, 2009·Anti-cancer Drugs·Gunjan GakharThu Annelise Nguyen
Dec 24, 2010·World Journal of Surgical Oncology·Michael StamatakosKonstantinos Kontzoglou
Jan 18, 2013·PloS One·Karim WafaKishore B S Pasumarthi
Nov 17, 2015·International Journal of Molecular Sciences·Byeong Mo KimYonggeun Hong
Dec 8, 2009·The American Journal of Cardiology·Alaide ChieffoAttilio Maseri
Mar 22, 2007·British Journal of Cancer·C E S ComstockK E Knudsen
May 25, 2007·Nature Reviews. Cancer·Sayyed K ZaidiGary S Stein
May 13, 2018·BMC Cancer·Selvi KunnimalaiyaanMuthusamy Kunnimalaiyaan
Dec 3, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Fei WuJia-Ju Lu
Jun 13, 2015·The Journal of Reproduction and Development·Mohamed M'bayeLiguo Yang
Apr 20, 2011·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Dewei JiaJing Liu
Sep 12, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Dariusz RozkiewiczDariusz Pawlak
Mar 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ke XuWenfa Lu
Jun 19, 2012·Clinical Epigenetics·Zhi-Yi GuoFang Yang
Feb 24, 2011·Cancer Research·Guergana TchakarskaBrigitte Sola

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Methods Mentioned

BETA
confocal microscopy
fluorescence microscopy
transfection

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