특별세미나_권소희 교수님(연세대)

올해의 마지막 세미나로 최근에 재미있는 논문을 발표하신 연세대학교 약학대학의 권소희 교수님을 초대했습니다. 

아래의 URL을 통해서 참여해 주시면 됩니다. 

https://kangwon-ac-kr.zoom.us/j/82860650721 

시간은 2020년 12월 18일(화) 오전11시입니다. 

HPV-mediated nuclear export of HP1γ drives cervical tumorigenesis by downregulation of p53

권소희 교수(연세대학교 약학대학)

E6 oncoprotein derived from high-risk human papillomavirus (HPV) drives the development of cervical cancer through p53 degradation. Because cervical cancer therapies to inactivate HPV or E6 protein are not available, alternative strategies are required. Here, we show that HPV-mediated nuclear export of human heterochromatin protein 1γ (HP1γ) reduces the stability of p53 through UBE2L3-mediated p53 polyubiquitination during cervical cancer progression. In general, HP1 plays a key role in heterochromatin formation and transcription in the nucleus. However, our immunostaining data showed that the majority of HP1γ is localized in the cytoplasm in HPV-mediated cervical cancer. We found that HPV E6 protein drives unusual nuclear export of HP1γ through the interaction between the NES sequence of HP1γ and exportin-1. The mutation of the NES sequence in HP1γ led to nuclear retention of HP1γ and reduced cervical cancer cell growth and tumor generation. We further discovered that HP1γ directly suppresses the expression of UBE2L3 which drives E6-mediated proteasomal degradation of p53 in cervical cancer. Downregulation of UBE2L3 by overexpression of HP1γ suppressed UBE2L3-dependent p53 degradation-promoting apoptosis of cervical cancer cells. Our findings propose a useful strategy to overcome p53 degradation in cervical cancer through the blockage of nuclear export of HP1γ.

학력 및 약력

1995-1999   성균관대학교 약학대학, B.S.

1999-2001   성균관대학교 약학대학, M.S.

2002-2007   University of Basel & FMI, 스위스, Ph.D.

2007-2011   Stowers Institute for Medical Research (박사후연구원)

2011-현재    연세대학교 약학대학(조교수, 부교수)

주요발표논문 (최근)

Yi SA, Lee DH, Kim GW, Ryu HW, Park JW, Lee J, Han J, Park JH, Oh H, Lee J, Choi J, Kim HS, Kang HG, Kim DH, Chun KH, You JS, Han JW*, Kwon SH*. HPV-mediated nuclear export of HP1γ drives cervical tumorigenesis by downregulation of p53. Cell Death Differ. 2020 Sep;27(9):2537-2551.

Kiem PV, Nhiem NX, Anh NH, Yen DTH, Cuong NT, Tai BH, Yen PH, Nam NH, Minh CV, Chinh PT, Jeon YH, Park SJ, Kim SH, Kwon SH*. Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta. Bioorg Chem. 2020 Nov;104:104268.

Cho HY, Lee SW, Jeon YH, Lee DH, Kim GW, Yoo J, Kim SY, Kwon SH*. Combination of ACY-241 and JQ1 Synergistically Suppresses Metastasis of HNSCC via Regulation of MMP-2 and MMP-9. Int J Mol Sci. 2020 Sep 19;21(18):6873.

Yi SA, Kim GW, Yoo J, Han JW*, Kwon SH*. HP1γ Sensitizes Cervical Cancer Cells to Cisplatin through the Suppression of UBE2L3. Int J Mol Sci. 2020 Aug 19;21(17):E5976.

Kim GW, Yoo J, Won HR, Yeon SK, Lee SW, Lee DH, Jeon YH, Kwon SH*. A452, HDAC6-selective inhibitor synergistically enhances the anticancer activity of immunomodulatory drugs in IMiDs-resistant multiple myeloma. Leuk Res. 2020 Aug;95:106398. doi: 10.1016/j.leukres.2020.106398.

Yoo J, Jeon YH, Cho HY, Lee SW, Kim GW, Lee DH, Kwon SH*. Advances in Histone Demethylase KDM3A as a Cancer Therapeutic Target. Cancers (Basel). 2020 Apr 28;12(5). pii: E1098. doi: 10.3390/cancers12051098.