PMID- 15075260
OWN - NLM
STAT- MEDLINE
DCOM- 20041210
LR  - 20210526
IS  - 1535-9778 (Print)
IS  - 1535-9786 (Electronic)
IS  - 1535-9786 (Linking)
VI  - 3
IP  - 2
DP  - 2004 Apr
TI  - pdf1, a palmitoyl protein thioesterase 1 Ortholog in Schizosaccharomyces pombe: a 
      yeast model of infantile Batten disease.
PG  - 302-10
AB  - Infantile Batten disease is a severe neurodegenerative storage disorder caused by 
      mutations in the human PPT1 (palmitoyl protein thioesterase 1) gene, which 
      encodes a lysosomal hydrolase that removes fatty acids from lipid-modified 
      proteins. PPT1 has orthologs in many species, including lower organisms and 
      plants, but not in Saccharomyces cerevisiae. The fission yeast 
      Schizosaccharomyces pombe contains a previously uncharacterized open reading 
      frame (SPBC530.12c) that encodes the S. pombe Ppt1p ortholog fused in frame to a 
      second enzyme that is highly similar to a previously cloned mouse dolichol 
      pyrophosphatase (Dolpp1p). In the present study, we characterized this 
      interesting gene (designated here as pdf1, for palmitoyl protein 
      thioesterase-dolichol pyrophosphate phosphatase fusion 1) through deletion of the 
      open reading frame and complementation by plasmids bearing mutations in various 
      regions of the pdf1 sequence. Strains bearing a deletion of the entire pdf1 open 
      reading frame are nonviable and are rescued by a pdf1 expression plasmid. 
      Inactivating mutations in the Dolpp1p domain do not rescue the lethality, whereas 
      mutations in the Ppt1p domain result in cells that are viable but abnormally 
      sensitive to sodium orthovanadate and elevated extracellular pH. The latter 
      phenotypes have been previously associated with class C and class D vacuolar 
      protein sorting (vps) mutants and vacuolar membrane H(+)-ATPase (vma) mutants in 
      S. cerevisiae. Importantly, the Ppt1p-deficient phenotype is complemented by the 
      human PPT1 gene. These results indicate that the function of PPT1 has been widely 
      conserved throughout evolution and that S. pombe may serve as a genetically 
      tractable model for the study of human infantile Batten disease.
FAU - Cho, Steve K
AU  - Cho SK
AD  - Department of Internal Medicine and the Hamon Center for Therapeutic Oncology 
      Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, 
      USA.
FAU - Hofmann, Sandra L
AU  - Hofmann SL
LA  - eng
GR  - R01 NS035323/NS/NINDS NIH HHS/United States
GR  - NS35323/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Eukaryot Cell
JT  - Eukaryotic cell
JID - 101130731
RN  - 3WHH0066W5 (Vanadates)
RN  - 61H4T033E5 (Orotic Acid)
RN  - 7IA9OUC93E (5-fluoroorotic acid)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cloning, Molecular
MH  - Gene Deletion
MH  - Genetic Complementation Test
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - *Models, Genetic
MH  - Molecular Sequence Data
MH  - Neuronal Ceroid-Lipofuscinoses/*genetics
MH  - Orotic Acid/*analogs & derivatives/pharmacology
MH  - Point Mutation
MH  - Protein Processing, Post-Translational
MH  - Protein Structure, Tertiary
MH  - Schizosaccharomyces/*enzymology/genetics
MH  - Sequence Alignment
MH  - Thiolester Hydrolases/*genetics/metabolism
MH  - Vanadates/toxicity
PMC - PMC387660
EDAT- 2004/04/13 05:00
MHDA- 2004/12/16 09:00
PMCR- 2004/04/01
CRDT- 2004/04/13 05:00
PHST- 2004/04/13 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/04/13 05:00 [entrez]
PHST- 2004/04/01 00:00 [pmc-release]
AID - 0239 [pii]
AID - 10.1128/EC.3.2.302-310.2004 [doi]
PST - ppublish
SO  - Eukaryot Cell. 2004 Apr;3(2):302-10. doi: 10.1128/EC.3.2.302-310.2004.