PMID- 22888000
OWN - NLM
STAT- MEDLINE
DCOM- 20121231
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 41
DP  - 2012 Oct 5
TI  - Precise regulation of porcupine activity is required for physiological Wnt 
      signaling.
PG  - 34167-78
LID - 10.1074/jbc.M112.381970 [doi]
AB  - Gradients of diverse Wnt proteins regulate development, renewal, and 
      differentiation. Porcupine (PORCN) is a membrane-bound O-acyltransferase that is 
      required for post-translational modification of all Wnts to enable their 
      transport, secretion, and activity. Mutations in PORCN are associated with focal 
      dermal hypoplasia (FDH), whereas gene deletion causes embryonic lethality in 
      mice. To study the protein in more detail, zinc finger nucleases were used to 
      edit the PORCN genomic locus, establishing two HT1080 fibrosarcoma clones null 
      for PORCN activity that facilitate the study of PORCN structure and function. We 
      establish that PORCN is a key non-redundant node for the regulation of global Wnt 
      signaling because PORCN null cells are completely incapable of autocrine Wnt 
      signaling. The strength of Wnt signaling is exquisitely sensitive to PORCN 
      expression, with a dynamic range of at least 3 orders of magnitude, suggesting 
      that PORCN activity is a key modulator of all Wnt ligand activity. Consistent 
      with this, we find that multiple FDH-associated mutants have only subtle 
      alterations in enzyme activity yet are associated with a severe FDH phenotype. 
      These studies support an essential regulatory role of PORCN in shaping Wnt 
      signaling gradients.
FAU - Proffitt, Kyle D
AU  - Proffitt KD
AD  - Program in Cancer and Stem Cell Biology, Duke-National University of Singapore 
      Graduate Medical School, 8 College Road, 169857 Singapore.
FAU - Virshup, David M
AU  - Virshup DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120810
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Membrane Proteins)
RN  - 0 (Xenopus Proteins)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (Porcn protein, mouse)
SB  - IM
MH  - Acyltransferases
MH  - Animals
MH  - Cell Line, Tumor
MH  - Focal Dermal Hypoplasia/genetics/metabolism/pathology
MH  - Gene Expression Regulation/*physiology
MH  - Genetic Loci/*physiology
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Wnt Signaling Pathway/*physiology
MH  - Xenopus Proteins/genetics/*metabolism
MH  - Xenopus laevis
PMC - PMC3464525
EDAT- 2012/08/14 06:00
MHDA- 2013/01/01 06:00
PMCR- 2012/08/10
CRDT- 2012/08/14 06:00
PHST- 2012/08/14 06:00 [entrez]
PHST- 2012/08/14 06:00 [pubmed]
PHST- 2013/01/01 06:00 [medline]
PHST- 2012/08/10 00:00 [pmc-release]
AID - S0021-9258(20)62752-1 [pii]
AID - M112.381970 [pii]
AID - 10.1074/jbc.M112.381970 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Oct 5;287(41):34167-78. doi: 10.1074/jbc.M112.381970. Epub 2012 
      Aug 10.