PMID- 12909364
OWN - NLM
STAT- MEDLINE
DCOM- 20031010
LR  - 20190708
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 312
DP  - 2003 Jul 17
TI  - Characterization of Drosophila palmitoyl-protein thioesterase 1.
PG  - 271-9
AB  - Batten disease or neuronal ceroid lipofuscinoses (NCL) are a group of genetic 
      neurodegenerative diseases that primarily afflict infants and children and are 
      characterized by progressive loss of brain functions caused by the death of 
      central nervous system (CNS) neurons. The most severe form of the disease is 
      infantile NCL (INCL). INCL is caused by mutations in the palmitoyl-protein 
      thioesterase 1 (PPT1) gene, which encodes a palmitoyl-protein thioesterase 1 
      enzyme that cleaves long-chain fatty acids from S-acylated proteins within the 
      lysosome. How the loss of this activity causes the death of CNS neurons is not 
      known. A PPT1 homolog and palmitoyl-protein thioesterase 1 enzyme activity were 
      characterized in Drosophila melanogaster as an initial step in developing 
      Drosophila as a model system for studying the etiology of INCL. Predicted gene 
      CG12108 in region 8A2 of the X chromosome is 55% identical and 72% similar to 
      human PPT1 and contains conserved catalytic residues and sites of glycosylation. 
      Northern-blot hybridizations revealed a major 1.5 kb CG12108 transcript in 
      unfertilized eggs, embryos, larvae, pupae, adult head and thorax, ovary, testis, 
      and S2 tissue culture cells, as well as several minor mRNA species in some 
      tissues. Levels of the 1.5 kb transcript were fairly uniform among tissues except 
      in testis, where the transcript was enriched 5-fold. The same tissues also 
      contained palmitoyl-protein thioesterase 1 enzyme activity measured using the 
      fluorometric substrate 4-methylumbelliferyl-6-thiopalmitoyl-beta-D-glucoside. 
      Enzyme activity was highest in testis and varied among the other tissues to a 
      greater extent than did CG12108 message, suggesting that CG12108 is subjected to 
      post-transcriptional regulation. Finally, flies homozygous for a deletion that 
      removes CG12108 and three unrelated neighboring genes had less than 3% of 
      wildtype levels of enzyme activity, consistent with CG12108 encoding functional 
      palmitoyl-protein thioesterase 1 activity and being the fly ortholog of human 
      PPT1. CG12108 has been appropriately renamed Ppt1.
FAU - Glaser, Robert L
AU  - Glaser RL
AD  - Wadsworth Center, New York State Department of Health, P.O. Box 22002, Albany, NY 
      12201-2002, USA. glaser@wadsworth.org
FAU - Hickey, Anthony J
AU  - Hickey AJ
FAU - Chotkowski, Heather L
AU  - Chotkowski HL
FAU - Chu-LaGraff, Quynh
AU  - Chu-LaGraff Q
LA  - eng
GR  - NS44572/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (RNA, Messenger)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Line
MH  - Drosophila/cytology/*enzymology/genetics
MH  - Embryo, Nonmammalian/enzymology/metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Gene Expression Regulation, Enzymologic
MH  - Genes, Insect/genetics
MH  - Humans
MH  - Male
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - RNA, Messenger/genetics/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Thiolester Hydrolases/chemistry/*genetics/metabolism
EDAT- 2003/08/12 05:00
MHDA- 2003/10/11 05:00
CRDT- 2003/08/12 05:00
PHST- 2003/08/12 05:00 [pubmed]
PHST- 2003/10/11 05:00 [medline]
PHST- 2003/08/12 05:00 [entrez]
AID - S0378111903006231 [pii]
AID - 10.1016/s0378-1119(03)00623-1 [doi]
PST - ppublish
SO  - Gene. 2003 Jul 17;312:271-9. doi: 10.1016/s0378-1119(03)00623-1.