PMID- 10658183
OWN - NLM
STAT- MEDLINE
DCOM- 20000225
LR  - 20071114
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 59
IP  - 1
DP  - 2000 Jan 1
TI  - In vitro depalmitoylation of neurospecific peptides: implication for infantile 
      neuronal ceroid lipofuscinosis.
PG  - 32-8
AB  - Palmitoyl protein thioesterase 1 (PPT1) removes palmitate from specific cysteine 
      residues in peptides and proteins. We have previously shown that a palmitoylated 
      myelin glycoprotein. Po octapeptide (IRYCWLRR) can be specifically 
      depalmitoylated by PPT1 in vitro (Cho and Dawson [1998] J. Neurochem. 171 
      ;323-329). To characterize further the substrate specificity of PPT1, we prepared 
      various palmitoylated oligopeptides, based on palmitoylated sequences from 
      different proteins. A truncated tetrapeptide from Po (RY[palmitoyl]-CW) was as 
      good a substrate as the octapeptide Po, with optimal activity at pH 4.0. In 
      contrast, other peptide substrates showed marked differences. Thus, the 
      deacylation of GAP-43 (MLCCMRR), rhodopsin (VTTLCCGKN), and Galpha subunit 
      (MGCLGNSK) peptides was more efficient at neutral pH (7.4) than at acidic pH 
      (4.0), with the greatest efficiency toward the Galpha peptide (five- to sixfold 
      higher than other substrates). Infantile neuronal ceroid lipofuscinosis (INCL) is 
      caused by PPT1 deficiency, and the absence of enzymatic activity was confirmed 
      with GAP-43 peptide as well as the Po peptide. LA-N-5 human neuroblastoma cells 
      overexpressing PPT1 showed increased depalmitoylation of all the peptide 
      substrates, indicating that these peptides are deacylated by PPT1. An amide 
      derivative of a palmitoylated K-Ras peptide (AcG-palmitoyl diamino 
      propionate-VKIKK) acted as an enzyme pseudosubstrate and inhibited PPT1 enzyme 
      activity in a dose-dependent manner. The peptide itself (AcGCVKIKK) did not 
      affect PPT activity. In summary, PPT1 is able to hydrolyze a range of cysteinyl 
      peptide sequences found in both neuron-specific and ubiquitous (e.g., Galpha) 
      proteins. The inhibitor of PPT1 activity should facilitate the development of a 
      model for INCL and help explain the neuronal death in this disease.
FAU - Cho, S
AU  - Cho S
AD  - Department of Pediatrics, University of Chicago Medical School, Illinois 60637, 
      USA.
FAU - Dawson, P E
AU  - Dawson PE
FAU - Dawson, G
AU  - Dawson G
LA  - eng
GR  - NS-36866/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  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Neuropeptides)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Brain Neoplasms/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Hydrolysis
MH  - Infant, Newborn
MH  - Neuroblastoma/metabolism
MH  - Neuronal Ceroid-Lipofuscinoses/*metabolism
MH  - Neuropeptides/*metabolism
MH  - Thiolester Hydrolases/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2000/02/05 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - 10.1002/(SICI)1097-4547(20000101)59:1<32::AID-JNR5>3.0.CO;2-A [pii]
PST - ppublish
SO  - J Neurosci Res. 2000 Jan 1;59(1):32-8.