Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue

Charles F. Thomas, Robert A Anders, Michael P. Gustafson, Edward B. Leof, Andrew H. Limper

Research output: Contribution to journalArticle

Abstract

Pneumocystis carinii causes life-threatening pneumonia in immunocompromised patients. The inability to culture P. carinii has hampered basic investigations of the organism's life cycle, limiting the development of new therapies directed against it. Recent investigations indicate that P. carinii is a fungus phylogenetically related to other ascomycetes such as Schizosaccharomyces pombe. The cell cycles of S. pombe and homologous fungi are carefully regulated by cell-division-cycle molecules (cdc), particularly cell-division-cycle 2 (Cdc2), a serine-threonine kinase with essential activity at the G1 restriction point and for entry into mitosis. Antibodies to the proline-serine-threonine-alanine-isoleucine-arginine (PSTAIR) amino-acid sequence conserved in Cdc2 proteins specifically precipitated, from P. carinii extracts, a molecule with kinase activity consistent with a Cdc2-like protein. Cdc2 molecules exhibit differential activity throughout the life cycle of the organisms in which they occur. In accord with this, the P. carinii Cdc2 showed greater specific activity in P. carinii trophic forms (trophozoites) than in spore-case forms (cysts). In addition, complete genomic and complementary DNA (cDNA) sequences of P. carinii Cdc2 were cloned and found to be most closely homologus to the corresponding sequences of other pathogenic fungi. The function of P. carinii cdc2 cDNA was further documented through its ability to complement the DNA of mutant strains of S. pombe with temperature-sensitive deficiencies in Cdc2 activity. The P. carinii cdc2 cDNA restored normal Cdc2 function in these mutant strains of S. pombe, and promoted fungal proliferation. These studies represent the first molecular analysis of the cell-cycle-regulatory machinery in P. carinii. Further understanding of P. carinii's life cycle promises novel insights for preventing and treating the intractable infection it causes in immunocompromised patients.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume18
Issue number3
StatePublished - 1998
Externally publishedYes

Fingerprint

Pneumocystis carinii
Fungi
Life cycle
Cell Cycle
Complementary DNA
Molecules
Cells
Schizosaccharomyces
Isoleucine
Protein-Serine-Threonine Kinases
DNA sequences
Threonine
Proline
Alanine
Serine
Life Cycle Stages
Machinery
Arginine
Proteins
Phosphotransferases

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue. / Thomas, Charles F.; Anders, Robert A; Gustafson, Michael P.; Leof, Edward B.; Limper, Andrew H.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 18, No. 3, 1998, p. 297-306.

Research output: Contribution to journalArticle

Thomas, Charles F. ; Anders, Robert A ; Gustafson, Michael P. ; Leof, Edward B. ; Limper, Andrew H. / Pneumocystis carinii contains a functional cell-division-cycle Cdc2 homologue. In: American Journal of Respiratory Cell and Molecular Biology. 1998 ; Vol. 18, No. 3. pp. 297-306.
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