Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma

Z. Liu, N. Lam, E. Wang, R. A. Virden, B. Pawel, E. F. Attiyeh, J. M. Maris, C. J. Thiele

Research output: Contribution to journalArticle

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Abstract

As a transcription factor, localization to the nucleus and the recruitment of cofactors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc-finger transcription factor CASZ1 to function as a neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized. Through alanine scanning, immunofluorescence cell staining and co-immunoprecipitation, we define a critical region at the CASZ1 N terminus (AAs 23-40) that mediates the CASZ1b nuclear localization and NuRD interaction. Furthermore, we identified a nuclear export signal (NES) at the N terminus (AAs 176-192) that contributes to CASZ1 nuclear-cytoplasmic shuttling in a chromosomal maintenance 1-dependent manner. An analysis of CASZ1 protein expression in a primary NB tissue microarray shows that high nuclear CASZ1 staining is detected in tumor samples from NB patients with good prognosis. In contrast, cytoplasmic-restricted CASZ1 staining or low nuclear CASZ1 staining is found in tumor samples from patients with poor prognosis. These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as NB tumorigenesis.

Original languageEnglish
Pages (from-to)97-109
Number of pages13
JournalOncogene
Volume36
Issue number1
DOIs
Publication statusPublished - 5 Jan 2017
Externally publishedYes

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Nuclear Export Signals
Neuroblastoma
Histone Deacetylases
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Staining and Labeling
Amino Acids
Neoplasms
Transcription Factors
Nucleosomes
Zinc Fingers
Immunoprecipitation
Alanine
Fluorescent Antibody Technique
Carcinogenesis
Maintenance
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma. / Liu, Z.; Lam, N.; Wang, E.; Virden, R. A.; Pawel, B.; Attiyeh, E. F.; Maris, J. M.; Thiele, C. J.

In: Oncogene, Vol. 36, No. 1, 05.01.2017, p. 97-109.

Research output: Contribution to journalArticle

Liu, Z, Lam, N, Wang, E, Virden, RA, Pawel, B, Attiyeh, EF, Maris, JM & Thiele, CJ 2017, 'Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma', Oncogene, vol. 36, no. 1, pp. 97-109. https://doi.org/10.1038/onc.2016.179
Liu, Z. ; Lam, N. ; Wang, E. ; Virden, R. A. ; Pawel, B. ; Attiyeh, E. F. ; Maris, J. M. ; Thiele, C. J. / Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma. In: Oncogene. 2017 ; Vol. 36, No. 1. pp. 97-109.
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