Document Detail


Cloning, characterization and identification of the gene encoding phosphatidylinositol 4-kinase.
MedLine Citation:
PMID:  9449533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The vast majority of AIDS-related deaths are associated with opportunistic infections. For fungal infections, there are few effective antifungals, particularly for systemic use. The discovery that very low doses of the bleomycin family of anticancer chemical congeners compromise the integrity of fungal cell walls led to our approach to identify genes that complement-cell wall defects, and develop methods to facilitate the identification of new antifungals targeted to fungal cell walls. This report describes one of the genes cloned by complementation of the blm1-1 mutation of S. cerevisiae using a YCp50-based yeast genomic library. Characterization and identification of the gene were carried out using drug screening tests, Southern hybridization analyses, DNA sequencing and DNA sequence similarity searches in databases. The gene STT4, is essential for viability and encodes a phosphatidylinositol 4-kinase that plays an important role in the phosphatidylinositol-mediated signal transduction pathway required for cell wall integrity. Like blm1-1 mutant strains, stt4 cells arrest mostly in the G2/M phase of the cell cycle. Further studies using this approach should help us understand the role of PI4-K in maintaining fungal cell-wall integrity, identify additional genes affecting potential target structures in cell walls of opportunistic fungal pathogens in AIDS patients, and assist in drug discovery and antifungal drug design.
Authors:
A Pramanik; E Garcia; R Ospina; M Powell; M Martinez; W Alejo; J McKoy; C W Moore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cellular and molecular biology (Noisy-le-Grand, France)     Volume:  43     ISSN:  0145-5680     ISO Abbreviation:  Cell. Mol. Biol. (Noisy-le-grand)     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-02-19     Completed Date:  1998-02-19     Revised Date:  2007-12-11    
Medline Journal Info:
Nlm Unique ID:  9216789     Medline TA:  Cell Mol Biol (Noisy-le-grand)     Country:  FRANCE    
Other Details:
Languages:  eng     Pagination:  1007-18     Citation Subset:  IM; X    
Affiliation:
Department of Microbiology and Immunology, City University of New York Medical School 10031, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 4-Kinase / genetics*
Bleomycin / metabolism
Cloning, Molecular
Drug Resistance, Microbial / genetics
Genes, Fungal*
Genetic Complementation Test
Mutation
Plasmids / chemistry,  genetics,  isolation & purification
Saccharomyces cerevisiae / enzymology*,  genetics*
Saccharomyces cerevisiae Proteins*
Transformation, Genetic
Chemical
Reg. No./Substance:
0/Saccharomyces cerevisiae Proteins; 11056-06-7/Bleomycin; EC 2.7.1.67/1-Phosphatidylinositol 4-Kinase; EC 2.7.1.67/PIK1 protein, S cerevisiae

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