ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation

Schneider-Gädicke, Ansbert; Beer-Romero, Peggy; Brown, Laura G.; Nussbaum, Robert L.; Page, David C.

doi:10.1016/0092-8674(89)90061-5

Cited by 282 publications

(124 citation statements)

References 34 publications

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“…All tumors samples from female patients showed evidence of expression of both alleles (wild type and mutant) in agreement with prior observations that ZFX escapes X-inactivation [22]. In addition, three of the ZFX mutation-bearing tumors were available for extraction of protein for western blot analysis.…”

Section: Resultssupporting

confidence: 67%

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Recurrent ZFX mutations in human sporadic parathyroid adenomas

Soong

Arnold

2014

Oncoscience

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ABSTRACT:The molecular abnormalities leading to sporadic parathyroid adenomas, a common type of human endocrine neoplasm, are heterogeneous and incompletely understood. Using whole exome and direct sequencing of parathyroid adenoma DNA samples, we identified recurrent somatic mutations in the ZFX gene. ZFX is a member of Krueppel C2H2 type zinc finger protein family, was initially described as a homolog of ZFY, and has been implicated as a transcription factor regulating embryonic stem cell renewal. The ZFX mutations we identified were strikingly specific, focused in each tumor on one encoded residue in a hotspot of two consecutive highly conserved arginine residues (R786/787; arginine to glutamine, threonine or leucine) in a zinc finger domain near the C-terminus of the protein. The intragenic specificity of these recurrently selected mutations, their confirmed expression within the tumors, the absence of loss of heterozygosity, and the absence of these mutations among over 4000 ZFX alleles in the dbSNP137 database, strongly suggest a novel role for ZFX as a human proto-oncogene. Further, these observations highlight the mutated zincfinger domain as a new focal point for understanding ZFX's normal and tumorigenic functions, and for development of molecularly-targeted therapeutics.

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Section: Resultssupporting

confidence: 67%

“…The encoded protein product includes 13 zinc finger domains [22]. The mutated residues identified in our series of parathyroid neoplasms are located in the zinc finger subdomain that may directly interact with DNA.…”

Section: Discussionmentioning

confidence: 99%

Recurrent ZFX mutations in human sporadic parathyroid adenomas

Soong

Arnold

2014

Oncoscience

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“…ZFX as a transcription factor would promote the transcription of downstream target genes such as growth factors or oncogenes. 20 Therefore, ZFX is believed to have an important role in tumor progression and pathogenesis. With the light of past research, this study was planned to find the effects of ZFX knockdown in prostate cancer cells as a therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9

et al. 2012

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Zinc finger protein X-linked (ZFX) is a highly conservative mammalian gene with related functions in cell survival and proliferation. However, there are limited reports on regulation of ZFX as a therapeutic target in cancer treatment. In this study, the expression of ZFX in prostate cancer with matched normal adjacent tissues (n ¼ 45) and benign prostatic hyperplasia (BPH) tissues (n ¼ 16) were observed by immunohistochemical analysis. The effect of lentiviral siRNA (small interference RNA)-mediated dysfunction of ZFX on the proliferation of prostate cancer cells was studied. ZFX mRNA and protein expression levels in prostate cancer cells (PC-3 and DU145) were analyzed by western blotting and real-time polymerase chain reaction (RT-PCR). The effects of siRNA targeting ZFX on growth, cell cycle and apoptosis of PC-3 cells were evaluated by MTT assay and flow cytometry. We also investigated the effect of ZFX deletion on the activation of caspase-1, -3 and -9 by western blotting and colorimetric assay. Prostate cancer specimens appeared significantly higher (42.2% of cases being positive) than that observed in normal adjacent tissues (11.8% of cases being positive) and BPH tissues (12.5% of cases being positive). Repression of ZFX in the prostate cancer cells effectively suppressed the cellular proliferation and colony-formation ability, and led to G1 phase cell cycle arrest. Moreover, inhibition of ZFX-induced cell apoptosis by activating caspase-1, -3 and -9. In conclusion, ZFX represents the prominent role in the progression of prostate cancer and may be a promising therapy target for prostate cancer.

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“…A busca por esse "gene" durou cerca de 30 anos e sua descoberta mostrou que os mecanismos genéti-cos da determinação sexual são ainda mais complexos do que se imaginava (13)(14)(15)(16).…”

Section: Biologia Molecular Da Determinação Do Sexounclassified

Genes envolvidos na determinação e diferenciação do sexo

Mello

Assumpção

Hackel

2005

Arq Bras Endocrinol Metab

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RESUMOO sexo cromossômico é estabelecido na fertilização pela presença de um cromossomo X ou Y. O desenvolvimento dos sexos masculino e feminino passa, num primeiro momento, pela especialização das gônadas em testículos ou ovários; os demais processos decorrem de efeitos secundários provocados pelos hormônios por elas produzidos. As etapas de determinação e diferenciação das gônadas em testícu-los ou em ovários e a diferenciação dos genitais externos masculinos ou femininos envolvem a expressão específica de uma cascata de genes. Esses genes, seus respectivos padrões de expressão, bem como seus envolvimentos na manifestação de patologias ligadas ao desenvolvimento gonadal e dos genitais externos serão abordados nesta revisão. ABSTRACT Genes Involved in Sex Determination and Differentiation.Chromosomal sex is established at fertilization by the presence of an X or Y chromosome. The first step of male and female development is gonadal specialization in testes or ovaries; all other processes that follow result from secondary effects produced by testis and ovary hormones. Gonadal determination and differentiation and the development of external genitalia involve time-and tissue-specific expression of genes forming a gene cascade. Those genes, their expression profile and their role in the pathological manifestations related to gonadal and external genitalia development will be discussed in this review. (Arq Bras Endocrinol Metab 2005;49/1:14-25 ) Keywords: Chromosome; Gene; Gonadal differentiation; Gonadal dysgenesis; Sex; SRY N OS SERES HUMANOS E NA MAIORIA DOS MAMÍFEROS, os processos de determinação e diferenciação sexuais estão intrinsecamente associados à presença ou à ausência do cromossomo Y no cariótipo (1,2). O evento pivô na determinação sexual é a especialização das gônadas; as demais diferenças entre os sexos são efeitos secundários devidos aos hormônios por elas produzidos (3). O processo como um todo é classicamente dividido em quatro etapas: a determinação do sexo cromossômico, que é estabelecida na fertilização; a diferenciação das gônadas em testículos ou em ovários; a diferenciação dos genitais internos e externos masculinos ou femininos a partir de estruturas indiferenciadas presentes no embrião, que é dependente da presença ou ausência de testículos; e a diferenciação sexual secundária, que é a resposta de vários tecidos aos hormônios produzidos pelas gônadas para completar o fenótipo sexual. Portanto, a expressão revisão

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ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation

Cited by 282 publications

References 34 publications

Recurrent ZFX mutations in human sporadic parathyroid adenomas

Recurrent ZFX mutations in human sporadic parathyroid adenomas

Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9

Genes envolvidos na determinação e diferenciação do sexo

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