PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21

Oncogene
F HuA P Rapoport

Abstract

PBK/TOPK (PDZ-binding kinase, T-LAK-cell-originated protein kinase) is a serine-threonine kinase that is overexpressed in a variety of tumor cells but its role in oncogenesis remains unclear. Here we show, by co-immunoprecipitation experiments and yeast two-hybrid analysis, that PBK/TOPK physically interacts with the tumor suppressor p53 through its DNA-binding (DBD) domain in HCT116 colorectal carcinoma cells that express wild-type p53. PBK also binds to p53 mutants carrying five common point mutations in the DBD domain. The PBK-p53 interaction appears to downmodulate p53 transactivation function as indicated by PBK/TOPK knockdown experiments, which show upregulated expression of the key p53 target gene and cyclin-dependent kinase inhibitor p21 in HCT116 cells, particularly after genotoxic damage from doxorubicin. Furthermore, stable PBK/TOPK knockdown cell lines (derived from HCT116 and MCF-7 cells) showed increased apoptosis, G(2)/M arrest and slower growth as compared to stable empty vector-transfected control cell lines. Gene microarray studies identified additional p53 target genes involved in apoptosis or cell cycling, which were differentially regulated by PBK knockdown. Together, these data suggest that increased level...Continue Reading

References

Jun 21, 1991·Science·S E KernB Vogelstein
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·S S LeeR T Javier
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·T KiyonoM Ishibashi
Dec 8, 1998·The Journal of Experimental Medicine·M MüllerP H Krammer
Jun 3, 1999·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·U PohlM Weller
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·S GaudetR A Lue
Mar 1, 2003·Cancer Letters·Hironobu HaradaTakanori Ohnishi
Aug 2, 2003·The Journal of Biological Chemistry·Maoxiang LiGen Sheng Wu
Dec 23, 2003·Cancer Biology & Therapy·Bart RikhofWafik S El-Deiry
Nov 16, 2004·Biochemical and Biophysical Research Communications·Suguru MatsumotoKiyofumi Gyo
Nov 18, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·J D DoughertyD H Geschwind
Jan 7, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thierry SoussiChristophe Béroud
Dec 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tatyana A ZykovaZigang Dong
Jan 24, 2007·Experimental Cell Research·William S BrooksDavid F Crawford
Apr 3, 2007·Oncogene·S StranoG Blandino
May 8, 2007·Biochemical and Biophysical Research Communications·Asit K NandiAaron P Rapoport
Aug 19, 2007·The Journal of Biological Chemistry·Begona SotAlan R Fersht
May 31, 2008·The Journal of Biological Chemistry·William S BrooksDavid F Crawford
Dec 4, 2009·The Journal of Biological Chemistry·Franz HagnHorst Kessler

❮ Previous
Next ❯

Citations

Aug 15, 2012·Journal of Proteome Research·Zhengguang GuoYouhe Gao
Dec 15, 2012·Leukemia Research·Fang HuAaron P Rapoport
Mar 10, 2015·Cancer Cell International·Xiaoyan DouQiong Lin
Jun 6, 2016·Biochemical and Biophysical Research Communications·Chunming DongHao Zhou
Jun 28, 2016·International Journal of Molecular Sciences·Chin-Fang ChangMing-Chih Chou
Nov 13, 2019·Cancer Medicine·Andrew T StefkaAndrzej J Jakubowiak
Sep 13, 2019·Science Translational Medicine·Ann LinJason M Sheltzer
Nov 20, 2015·Experimental Biology and Medicine·Xudong ZhangHongbo Hu
Oct 26, 2018·Cell Death & Disease·Katharine J HerbertGeoff S Higgins

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis