A role for Pin1 in mammalian germ cell development and spermatogenesis

Front Biosci. 2004 Sep 1:9:3248-56. doi: 10.2741/1476.

Abstract

The peptidyl-prolyl isomerase Pin1 is proposed to have diverse functions in many vital aspects of the cell. Despite the multitude of proteins targeted by Pin1 and the proposed regulatory role it plays in critical cellular functions, Pin1 is an essential gene in some eukaryotic organisms, but is dispensable in metazoans. In two genetic models, Candida albicans and Drosophila melanogaster, Pin1 participates in distinct developmental processes regulated by the MAPK pathway. Pin1-deficient mice exhibit decreased primordial germ cell proliferation during embryonic development, along with several degenerative or proliferative defects in the adult testis, retina, mammary gland, and brain. The combination of primordial germ cell deficit and spermatogonial depletion contributes to severe fertility defects in Pin1-null mice. Since growth factor activated MAPK pathways are vital to germ cell proliferation and differentiation, a role for Pin1 in mammalian germ cell development and spermatogenesis is discussed in the context of the Ras/MEK/MAPK pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins
  • Gene Expression Regulation, Developmental*
  • Germ Cells / metabolism*
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / physiology*
  • Phenotype
  • Sp1 Transcription Factor / metabolism
  • Spermatogenesis*
  • Tissue Distribution
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Sp1 Transcription Factor
  • Transcription Factors
  • Zfp148 protein, mouse
  • PIN1 protein, human
  • Peptidylprolyl Isomerase
  • Pin1 protein, mouse
  • dod protein, Drosophila