GAM/ZFp/ZNF512B is central to a gene sensor circuitry involving cell-cycle regulators, TGF{beta} effectors, Drosha and microRNAs with opposite oncogenic potentials.

Nucleic Acids Research
Esmerina TiliCarlo M Croce

Abstract

MicroRNAs (miRNAs) are small regulatory RNAs targeting multiple effectors of cell homeostasis and development, whose malfunctions are associated with major pathologies such as cancer. Herein we show that GAM/ZFp/ZNF512B works within an intricate gene regulatory network involving cell-cycle regulators, TGFβ effectors and oncogenic miRNAs of the miR-17-92 cluster. Thus, GAM impairs the transcriptional activation of the miR-17-92 promoter by c-Myc, downregulates miR-17-92 miRNAs differentially, and limits the activation of genes responsive to TGFβ canonical pathway. In contrast, TGFβ decreases GAM transcripts levels while differentially upregulating miR-17-92 miRNAs. In turn, miR-17, miR-20a and miR-92a-1 target GAM transcripts, thus establishing a feedback autoregulatory loop. GAM transcripts are also targeted by miRNAs of the let-7 family. GAM downregulates Drosha, the main effector of miRNA maturation in the nucleus, and interacts with it in a RNA-dependent manner. Finally, GAM modulates the levels of E2F1 and Ras, and increases apoptosis while reducing cell proliferation. We propose that GAM represents a new kind of vertebrate regulator aimed at balancing the opposite effects of regulators of cell homeostasis by increasing the...Continue Reading

References

Apr 10, 1999·Genes & Development·M KretzschmarJ Massagué
Sep 1, 2001·The Journal of Steroid Biochemistry and Molecular Biology·H EggertM Eggert
Mar 16, 2002·Science·Klas Kärre
Jun 18, 2003·Cell·Yigong Shi, Joan Massagué
Jul 3, 2004·Genome Research·Frédéric CollandJean-Michel Gauthier
Nov 9, 2004·Nature·Richard I GregoryRamin Shiekhattar
Mar 16, 2005·Cell·Steven M JohnsonFrank J Slack
Jun 10, 2005·Nature·Kathryn A O'DonnellJoshua T Mendell
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano VoliniaCarlo M Croce
Apr 4, 2006·Nucleic Acids Research·Junichi MinenoIkunoshin Kato
May 3, 2006·Biological & Pharmaceutical Bulletin·Yukihiro AkaoTomoki Naoe
Jun 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lin ZhangGeorge Coukos
Aug 1, 2006·Nature Genetics·Michael DewsAndrei Thomas-Tikhonenko
Oct 25, 2006·Nature Reviews. Cancer·George A Calin, Carlo M Croce
Dec 1, 2006·The Journal of Biological Chemistry·Yannick SylvestrePascal Chartrand
Dec 1, 2006·The Journal of Biological Chemistry·Keith WoodsScott M Hammond
Jun 15, 2007·Nature Structural & Molecular Biology·Sonia Guil, Javier F Cáceres
Jun 15, 2007·Molecular Cell·John TsangAlexander van Oudenaarden
Oct 12, 2007·Future Oncology·Esmerina TiliGeorge Adrian Calin
Feb 14, 2008·Nature Reviews. Molecular Cell Biology·Giovanni Stefani, Frank J Slack
Feb 23, 2008·Science·Srinivas R ViswanathanRichard I Gregory
Jun 13, 2008·Nature·Brandi N DavisAkiko Hata
Jul 30, 2008·Cell·Joan Massagué
Aug 5, 2008·Trends in Molecular Medicine·Ingo BüssingHelge Grosshans
Aug 30, 2008·Nature Clinical Practice. Rheumatology·Esmerina TiliCarlo M Croce
Oct 3, 2008·Cancer Research·Thales PapagiannakopoulosKenneth S Kosik
Nov 11, 2008·Molecular Cell·Gracjan MichlewskiJavier F Cáceres
Dec 6, 2008·Genes & Development·Fatih OzsolakDavid E Fisher
Feb 26, 2009·Cell·Andrea Ventura, Tyler Jacks
Mar 4, 2009·Nature Cell Biology·Julia WinterSven Diederichs

❮ Previous
Next ❯

Citations

Aug 17, 2011·Journal of Nucleic Acids·Esmerina Tili, Jean-Jacques Michaille
Jun 3, 2014·Journal of Hematology & Oncology·Justin J L WongJeff Holst
May 28, 2015·Journal of Cellular Physiology·Viktorija SokolovaMarco A Pierotti
May 23, 2012·Trends in Pharmacological Sciences·Henriett ButzAttila Patócs
Oct 5, 2015·The Journal of Molecular Diagnostics : JMD·Weixin WangKatherine R Calvo
Nov 16, 2012·Proteomics·Milagros J Tenga, Iulia M Lazar
Jun 2, 2015·Current Pharmacology Reports·Satish RamalingamShrikant Anant
Nov 13, 2012·Molecular Oncology·Purificación MuñozManel Esteller
Sep 23, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Esmerina Tili, Jean-Jacques Michaille
Jul 1, 2018·International Journal of Molecular Sciences·Hiroshi I Suzuki
Sep 5, 2015·Oncotarget·Esmerina TiliCarlo M Croce
Jul 23, 2020·Frontiers in Immunology·Yunzhen GaoJunfeng Zheng
Mar 24, 2018·International Journal of Molecular Medicine·Fei ZhuYongquan Shi

❮ Previous
Next ❯

Datasets Mentioned

BETA
AB033022

Methods Mentioned

BETA
GAM
transfection
PCR
Assay
PCRs
electrophoresis
immunoprecipitation
two-hybrid

Software Mentioned

Adobe Photoshop
TargetScan

Related Concepts

Related Feeds

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