Phospho-ΔNp63α-dependent regulation of autophagic signaling through transcription and micro-RNA modulation.

Cell Cycle
Yiping HuangEdward A Ratovitski

Abstract

Cisplatin was shown to induce the ataxia telangiectasia mutated (ATM)-dependent phosphorylation of tumor protein p63 isoform, (ΔNp63α), leading to a transcriptional regulation of specific genes implicated in the control of cell death of squamous cell carcinoma (SCC) cells. We previously observed that the cisplatin-induced phosphorylated (p)-ΔNp63α transcriptionally regulates the expression of specific microRNAs (miRNAs) in SCC cells. We found here that cisplatin exposure of SCC cells led to modulation of the members of the autophagic pathway, such as Atg1/Ulk1, Atg3, Atg4A, Atg5, Atg6/Becn1, Atg7, Atg9A and Atg10, by a direct p-ΔNp63α-dependent transcriptional regulation. We further found that specific miRNAs (miR-181a, miR-519a, miR-374a and miR-630), which are critical downstream targets of the p-ΔNp63α, modulated the protein levels of ATG5, ATG6/BECN1, ATG10, ATG12, ATG16L1 and UVRAG, adding another level of expression control for autophagic pathways in SCC cells upon cisplatin exposure. Our data support the notion that the cisplatin-induced p-ΔNp63α could regulate key pathways implicated in response of cancer cells to chemotherapeutics.

References

Jun 28, 2002·Cancer Cell·Meera PatturajanDavid Sidransky
Apr 30, 2003·Cell Death and Differentiation·M Oren
Jun 1, 2005·Experimental Cell Research·Daisuke FuruyaNaoki Watanabe
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano VoliniaCarlo M Croce
Apr 8, 2006·Cell Death and Differentiation·F Murray-ZmijewskiJ-C Bourdon
Sep 23, 2006·Cell Death and Differentiation·M J AbedinA Kelekar
Sep 26, 2006·Nature Cell Biology·Shida YousefiHans-Uwe Simon
Nov 15, 2006·Autophagy·Diane CrightonKevin M Ryan
Nov 16, 2006·Autophagy·Chengyu LiangJae U Jung
Jan 19, 2007·Nature Reviews. Genetics·Kevin Chen, Nikolaus Rajewsky
Feb 17, 2007·Cell Death and Differentiation·D CrightonK M Ryan
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Jul 6, 2007·Autophagy·Noboru Mizushima, Tamotsu Yoshimori
Jul 7, 2007·Molecular Cell·Andrew GrimsonDavid P Bartel
Jul 13, 2007·Nature Reviews. Cancer·Lloyd Kelland
Sep 25, 2007·Nature Cell Biology·Yoshinori TakahashiHong-Gang Wang
Dec 26, 2007·Nucleic Acids Research·Doron BetelChris Sander
Jan 24, 2008·Autophagy·Deborah L Berry, Eric H Baehrecke
Feb 8, 2008·American Journal of Physiology. Renal Physiology·Cheng YangGur P Kaushal
Mar 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xinbin GuJoseph A Califano
May 24, 2008·Autophagy·Beth LevineGuido Kroemer
Jul 8, 2008·Autophagy·Ezgi TasdemirGuido Kroemer
Sep 2, 2008·Autophagy·Daniel J KlionskyDavid C Rubinsztein
Sep 23, 2008·Cell Death and Differentiation·M C MaiuriG Kroemer
Nov 13, 2008·Autophagy·Jennifer M Rosenbluth, Jennifer A Pietenpol
Feb 19, 2009·Autophagy·Eisuke Itakura, Noboru Mizushima
Mar 28, 2009·Cell Death and Differentiation·A Eisenberg-LernerA Kimchi
Apr 4, 2009·The Journal of Biological Chemistry·Ashley J Pratt, Ian J MacRae
Aug 7, 2009·Apoptosis : an International Journal on Programmed Cell Death·Yusuke KusamaKenichi Yoshida
Oct 6, 2009·Current Topics in Microbiology and Immunology·Zhifen Yang, Daniel J Klionsky
Dec 1, 2009·Current Opinion in Cell Biology·Chengyu Liang, Jae U Jung
Dec 17, 2009·Clinical and Experimental Nephrology·Kosuke InoueYoshio Terada
Feb 4, 2010·The EMBO Journal·Maria Chiara MaiuriGuido Kroemer
Mar 2, 2010·Cancer Biotherapy & Radiopharmaceuticals·Jing-Hua RenGang Wu
Mar 4, 2010·Journal of Cellular and Molecular Medicine·L Harhaji-TrajkovicV Trajkovic

❮ Previous
Next ❯

Citations

Mar 21, 2013·Molecular and Cellular Biochemistry·Tao JiangShiping Ding
Jun 4, 2013·Seminars in Cancer Biology·Federico PietrocolaGuido Kroemer
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Jens FüllgrabeBertrand Joseph
Aug 21, 2012·Carcinogenesis·Lisa B Frankel, Anders H Lund
Oct 20, 2012·Endocrine-related Cancer·Justin S GundaraStan B Sidhu
May 31, 2014·BioMed Research International·Rossella TitoneCiro Isidoro
May 23, 2014·Apoptosis : an International Journal on Programmed Cell Death·Y ChenY Q Wei
Oct 16, 2014·BioMed Research International·Joanna Magdalena Zarzynska
Apr 14, 2012·Leukemia & Lymphoma·Evguenia M Alexandrova, Ute M Moll
May 7, 2014·Oral Diseases·Mk SannigrahiM Khullar
Oct 21, 2014·Cell Proliferation·Y ChenL Ouyang
Sep 18, 2014·Photochemistry and Photobiology·Deeba N SyedDeeba N Syed
Jul 2, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Dake ChuGang Ji
Dec 21, 2012·Cell Cycle·Yemin Wang, Toshi Taniguchi
Jan 17, 2013·Autophagy·Kumsal Ayse TekirdagDevrim Gozuacik
Dec 21, 2012·Cell Cycle·Haiyan ZhaiJingfang Ju
Feb 21, 2014·Cell Cycle·Fanyan Meng, Guojun Wu
Aug 21, 2013·Cell Metabolism·Celia R BerkersKaren H Vousden
Jan 9, 2016·ScienceOpen Research·Yongfei Yang, Chengyu Liang
Feb 6, 2015·The Journal of Clinical Investigation·Álvaro F Fernández, Carlos López-Otín
Nov 29, 2013·Cancer Cell International·Bin ZhangJunye Liu
Apr 26, 2017·Autophagy·Jian ZhangDa Pang
Aug 17, 2016·Journal of Cell Science·Jens FüllgrabeDavid C Rubinsztein
Nov 3, 2017·BioMed Research International·Chao ChenPeifeng Li
Oct 29, 2013·Endocrine-related Cancer·Federica MoraniCiro Isidoro
Apr 24, 2019·Aging and Disease·Saumyendra N SarkarJames W Simpkins

❮ Previous
Next ❯

Methods Mentioned

BETA
ChIP
PCR
immunoprecipitation
Assay
transfection
Transmission

Software Mentioned

LightSwitch Pro Reporter System
TargetScan
AllStars
miRanda

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.