The expression and function of PAX3 in development and disease

Gene. 2018 Aug 5:666:145-157. doi: 10.1016/j.gene.2018.04.087. Epub 2018 May 4.

Abstract

The PAX3 gene encodes a member of the PAX family of transcription factors that is characterized by a highly conserved paired box motif. The PAX3 protein is a transcription factor consisting of an N-terminal DNA binding domain (containing a paired box and homeodomain) and a C-terminal transcriptional activation domain. This protein is expressed during development of skeletal muscle, central nervous system and neural crest derivatives, and regulates expression of target genes that impact on proliferation, survival, differentiation and motility in these lineages. Germline mutations of the murine Pax3 and human PAX3 genes cause deficiencies in these developmental lineages and result in the Splotch phenotype and Waardenburg syndrome, respectively. Somatic genetic rearrangements that juxtapose the PAX3 DNA binding domain to the transcriptional activation domain of other transcription factors deregulate PAX3 function and contribute to the pathogenesis of the soft tissue cancers alveolar rhabdomyosarcoma and biphenotypic sinonasal sarcoma. The wild-type PAX3 protein is also expressed in other cancers related to developmental lineages that normally express this protein and exerts phenotypic effects related to its normal developmental role.

Keywords: Alternative splicing; Central nervous system development; Fusion oncoprotein; Homeodomain; Melanocyte; Melanoma; Neural crest; Paired box; Rhabdomyosarcoma; Skeletal muscle development; Soft tissue sarcoma; Splotch; Target gene; Transcription factor; Waardenburg syndrome.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation
  • PAX3 Transcription Factor / genetics*
  • PAX3 Transcription Factor / metabolism
  • Sarcoma / genetics
  • Waardenburg Syndrome / genetics

Substances

  • PAX3 Transcription Factor
  • PAX3 protein, human