Prolyl isomerase Pin1 downregulates tumor suppressor RUNX3 in breast cancer.

Oncogene
Y-H Nicole TsangL-F Chen

Abstract

Emerging evidence demonstrates that RUNX3 is a tumor suppressor in breast cancer. Inactivation of RUNX3 in mice results in spontaneous mammary gland tumors, and decreased or silenced expression of RUNX3 is frequently found in breast cancer cell lines and human breast cancer samples. However, the underlying mechanism for initiating RUNX3 inactivation in breast cancer remains elusive. Here, we identify prolyl isomerase Pin1, which is often overexpressed in breast cancer, as a key regulator of RUNX3 inactivation. In human breast cancer cell lines and breast cancer samples, expression of Pin1 inversely correlates with the expression of RUNX3. In addition, Pin1 recognizes four phosphorylated Ser/Thr-Pro motifs in RUNX3 via its WW domain. Binding of Pin1 to RUNX3 suppresses the transcriptional activity of RUNX3. Furthermore, Pin1 reduces the cellular levels of RUNX3 in an isomerase activity-dependent manner by inducing the ubiquitination and proteasomal degradation of RUNX3. Knocking down Pin1 enhances the cellular levels and transcriptional activity of RUNX3 by inhibiting the ubiquitination and degradation of RUNX3. Our results identify Pin1 as a new regulator of RUNX3 inactivation in breast cancer.

References

May 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·F M DavisP N Rao
Nov 28, 2001·The Journal of Biological Chemistry·Pei-Jung LuKun Ping Lu
Jan 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yih-Cherng LiouKun Ping Lu
Nov 29, 2002·The EMBO Journal·Lin-feng ChenWarner C Greene
Mar 13, 2003·Breast Cancer Research : BCR·Gerburg WulfKun Ping Lu
May 28, 2003·Biochemical and Biophysical Research Communications·Jeum Soon BaeJaeHun Cheong
Oct 17, 2003·Life Sciences·Dao-Hai ZhangEvelyn Siew-Chuan Koay
Apr 28, 2004·The American Journal of Pathology·Lere BaoDa-Gong Wang
May 4, 2005·Nature Cell Biology·Gerburg WulfKun Ping Lu
Sep 20, 2007·Nature Reviews. Molecular Cell Biology·Kun Ping Lu, Xiao Zhen Zhou
Sep 22, 2007·Journal of Cellular Physiology·Boris J CheskisLeonard P Freedman
Dec 6, 2007·Journal of Korean Medical Science·Ki Tae HwangDong Young Noh
Feb 8, 2008·Breast Cancer Research and Treatment·Manish Mani SubramaniamThomas Choudary Putti
Jun 27, 2008·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Ying JiangJingshu Geng
Jul 22, 2008·Advances in Experimental Medicine and Biology·Alison J ButtRobert L Sutherland
Jan 6, 2009·The Journal of Biological Chemistry·Ayako NakanoTakeshi Imamura
Jan 20, 2009·Nature Cell Biology·Alessandra RustighiGiannino Del Sal
Aug 18, 2009·Biochimica Et Biophysica Acta·Manish Mani SubramaniamManuel Salto-Tellez
Aug 20, 2010·Cold Spring Harbor Perspectives in Biology·Eva Y H P Lee, William J Muller
Aug 20, 2011·Trends in Biochemical Sciences·Yih-Cherng LiouKun Ping Lu
Oct 7, 2011·Journal of Cellular Biochemistry·Fei ChenCheng Zhang
Nov 9, 2011·Molecular and Cellular Biology·Prashant RajbhandariElaine T Alarid

❮ Previous
Next ❯

Citations

Apr 11, 2013·Journal of Molecular Histology·Zhi-Kun BaiZhan-Peng Yue
May 28, 2013·Oncology Reports·Yang YangChuan-Dong Cheng
Aug 16, 2014·Cell Research·Zhimin Lu, Tony Hunter
Nov 8, 2014·Clinical and Experimental Pharmacology & Physiology·Muhamad A RostamNarin Osman
Nov 28, 2012·International Journal of Cancer. Journal International Du Cancer·Linda Shyue Huey ChuangYoshiaki Ito
Dec 7, 2013·Acta Crystallographica. Section D, Biological Crystallography·David E MortensonKatrina T Forest
Dec 3, 2014·Biochimica Et Biophysica Acta·Steven D Hanes
Aug 1, 2015·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yuan-Gui HuYi Li
Jun 28, 2013·Cell Cycle·Toshihisa Komori
Jan 3, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jing-Zhang WangYong Zhang
Jun 4, 2016·Nature Reviews. Cancer·Xiao Zhen Zhou, Kun Ping Lu
Aug 31, 2016·Archives of Pharmacal Research·Sang-Hyun MinKun Ping Lu
Jun 20, 2017·Small GTPases·Arun KumarGanesh Venkatraman
Apr 9, 2020·Frontiers in Cell and Developmental Biology·Xiangming Hu, Lin-Feng Chen
Apr 17, 2020·Frontiers in Cell and Developmental Biology·Wenchen PuYong Peng
Feb 17, 2017·Therapeutic Advances in Medical Oncology·Francesco Angelucci, Jakub Hort
Aug 31, 2018·Cell Death & Disease·Yang ChenYing-Bin Yang
Apr 4, 2021·Biomedicines·Hsiang-Hao ChuangChih-Jen Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
pull-down
co-immunoprecipitation
transfection
ubiquitination
acetylation
PCR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.