Characterization of critical domains within the tumor suppressor CASZ1 required for transcriptional regulation and growth suppression.

Molecular and Cellular Biology
Ryan A VirdenZhihui Liu

Abstract

CASZ1 is a zinc finger (ZF) transcription factor that is critical for controlling the normal differentiation of subtypes of neural and cardiac muscle cells. In neuroblastoma tumors, loss of CASZ1 is associated with poor prognosis and restoration of CASZ1 function suppresses neuroblastoma tumorigenicity. However, the key domains by which CASZ1 transcription controls developmental processes and neuroblastoma tumorigenicity have yet to be elucidated. In this study, we show that loss of any one of ZF1 to ZF4 resulted in a 58 to 79% loss in transcriptional activity, as measured by induction of tyrosine hydroxylase promoter-luciferase activity, compared to that of wild-type (WT) CASZ1b. Mutation of ZF5 or deletion of the C-terminal sequence of amino acids (aa) 728 to 1166 (a truncation of 38% of the protein) does not significantly alter transcriptional function. A series of N-terminal truncations reveals a critical transcriptional activation domain at aa 31 to 185 and a nuclear localization signal at aa 23 to 29. Soft agar colony formation assays and xenograft studies show that WT CASZ1b is more active in suppressing neuroblastoma growth than CASZ1b with a ZF4 mutation or a deletion of aa 31 to 185. This study identifies key domains ...Continue Reading

References

Dec 1, 1993·Molecular and Cellular Biology·H Matsushima, E Bogenmann
Nov 6, 1998·The Journal of Experimental Medicine·V De LaurenziG Melino
May 4, 2001·Mechanisms of Development·R HitierT Préat
Mar 4, 2003·Nature Reviews. Cancer·Garrett M Brodeur
Jul 26, 2003·Cancer Letters·Carmel M McConville, Joan Forsyth
Jun 1, 2005·Cancer Letters·Alexander SchrammAngelika Eggert
Apr 25, 2006·Biochemical and Biophysical Research Communications·Zhihui LiuCarol J Thiele
May 18, 2006·Molecular and Cellular Biology·Gerson RothschildAnna Lasorella
Sep 19, 2006·Genes & Development·Ruth GrosskortenhausChris Q Doe
Nov 14, 2006·Current Opinion in Pediatrics·Matthew R Grimmer, William A Weiss
Apr 16, 2008·Developmental Cell·Kathleen S Christine, Frank L Conlon
Apr 17, 2008·Cancer Research·Anindya Bagchi, Alea A Mills
Aug 16, 2008·Molecular BioSystems·Paul BrennanSaman Hewamana
Jan 15, 2009·International Journal of Cancer. Journal International Du Cancer·Johannes H SchulteAngelika Eggert
Mar 12, 2009·Current Cancer Drug Targets·Michael A GrotzerAlexandre Arcaro
Sep 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carol J ThieleAmy E McKee
Feb 27, 2010·Developmental Neurobiology·Liraz HarelMike Fainzilber
Jun 19, 2010·The New England Journal of Medicine·John M Maris
Mar 8, 2011·Molecular Neurobiology·Richard KillickMassimiliano Agostini

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Citations

Mar 26, 2013·Inorganic Chemistry·Angelique N BesoldSarah L J Michel
Mar 19, 2014·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Nirav M AminFrank L Conlon
Dec 20, 2018·Genome Research·Maura L GillisonDavid E Symer
Jan 19, 2017·Clinical Chemistry and Laboratory Medicine : CCLM·Xing-Biao QiuYi-Qing Yang
Sep 19, 2017·NPJ Genomic Medicine·David B NyerKarmella A Haynes

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