Human sex reversal due to impaired nuclear localization of SRY: A clinical correlation

Biaoru Li, Wei Zhang, Ging Chan, Agnes Jancso-Radek, Shunhe Liu, Michael A. Weiss

Research output: Contribution to journalArticle

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Abstract

SRY, an architectural transcription factor encoded by the sex-determining region of the Y chromosome, initiates testicular differentiation in mammalian embryogenesis. The protein contains a high-mobility group (HMG) box, a DNA-bending motif conserved among a broad class of nuclear proteins. Mutations causing human sex reversal (46, XY pure gonadal dysgenesis) are clustered in this domain. Basic N- and C-terminal regions of the HMG box are each proposed to provide nuclear localization signals. The significance of the C-terminal basic cluster (SRY residues 130-134) is uncertain, however, as its activity in cell culture varies with assay conditions. To test its importance, we have investigated a C-terminal sex-reversal mutation (R133W, position 78 of the HMG box). This de novo mutation impairs nuclear localization but not specific DNA binding or sharp DNA bending. Correlation between these properties and the phenotype of the patient suggests that nuclear localization of SRY is required for testicular differentiation and directed in part by the C-terminal basic cluster. To our knowledge, these results provide the first example of impaired organogenesis due to a nuclear localization signal mutation.

Original languageEnglish (US)
Pages (from-to)46480-46484
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number49
DOIs
StatePublished - Dec 7 2001

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46,XY Gonadal Dysgenesis
Nuclear Localization Signals
Mutation
DNA
Chromosomes
Nuclear Proteins
Cell culture
Nucleotide Motifs
Organogenesis
Y Chromosome
Assays
Transcription Factors
Embryonic Development
Cell Culture Techniques
Phenotype
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Human sex reversal due to impaired nuclear localization of SRY : A clinical correlation. / Li, Biaoru; Zhang, Wei; Chan, Ging; Jancso-Radek, Agnes; Liu, Shunhe; Weiss, Michael A.

In: Journal of Biological Chemistry, Vol. 276, No. 49, 07.12.2001, p. 46480-46484.

Research output: Contribution to journalArticle

Li, Biaoru ; Zhang, Wei ; Chan, Ging ; Jancso-Radek, Agnes ; Liu, Shunhe ; Weiss, Michael A. / Human sex reversal due to impaired nuclear localization of SRY : A clinical correlation. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 49. pp. 46480-46484.
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