PMID- 10051602
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 5
DP  - 1999 Mar 2
TI  - Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme
      phytanoyl-COA alpha-hydroxylase is a new FKBP-associated protein.
PG  - 2104-9
AB  - FKBP52 (FKBP59, FKBP4) is a "macro" immunophilin that, although sharing high
      structural and functional homologies in its amino-terminal domain with FKBP12
      (FKBP1), does not have immunosuppressant activity when complexed with FK506,
      unlike FKBP12. To investigate the physiological function of FKBP52, we used the
      yeast two-hybrid system as an approach to find its potential protein partners
      and, from that, its cellular role. This methodology, which already has allowed us
      to find the FK506-binding protein (FKBP)-associated protein FAP48, also led to
      the detection of another FKBP-associated protein. Determination of the sequence
      of this protein permitted its identification as phytanoyl-CoA alpha-hydroxylase
      (PAHX), a peroxisomal enzyme that so far was unknown as an FKBP-associated
      protein. Inactivation of this enzyme is responsible for Refsum disease in humans.
      The protein also corresponds to the mouse protein LN1, which could be involved in
      the progress of lupus nephritis. We show here that PAHX has the physical capacity
      to interact with the FKBP12-like domain of FKBP52, but not with FKBP12,
      suggesting that it is a particular and specific target of FKBP52. Whereas the
      binding of calcineurin to FKBP12 is potentiated by FK506, the specific
      association of PAHX and FKBP52 is maintained in the presence of FK506. This
      observation suggests that PAHX is a serious candidate for studying the cellular
      signaling pathway(s) involving FKBP52 in the presence of immunosuppressant drugs.
FAU - Chambraud, B
AU  - Chambraud B
AD  - Institut National de la Sante et de la Recherche Medicale (U488) and College de
      France, 80 rue du General Leclerc, 94276 Bicetre Cedex, France.
FAU - Radanyi, C
AU  - Radanyi C
FAU - Camonis, J H
AU  - Camonis JH
FAU - Rajkowski, K
AU  - Rajkowski K
FAU - Schumacher, M
AU  - Schumacher M
FAU - Baulieu, E E
AU  - Baulieu EE
LA  - eng
SI  - GENBANK/AF112977
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Primers)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.- (PHYH protein, human)
RN  - EC 1.14.- (Phyh protein, mouse)
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - EC 5.2.1.8 (Immunophilins)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - DNA Primers
MH  - Gene Library
MH  - Humans
MH  - Immunophilins/*genetics/metabolism
MH  - Jurkat Cells
MH  - Lupus Nephritis/*enzymology/genetics
MH  - Mice
MH  - Microbodies/enzymology
MH  - Mixed Function Oxygenases/*genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - Recombinant Fusion Proteins/biosynthesis/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Refsum Disease/*enzymology/genetics
MH  - Saccharomyces cerevisiae
MH  - Tacrolimus/metabolism/pharmacology
MH  - Tacrolimus Binding Proteins
PMC - PMC26744
EDAT- 1999/03/03 00:00
MHDA- 1999/03/03 00:01
CRDT- 1999/03/03 00:00
PHST- 1999/03/03 00:00 [pubmed]
PHST- 1999/03/03 00:01 [medline]
PHST- 1999/03/03 00:00 [entrez]
AID - 10.1073/pnas.96.5.2104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2104-9. doi: 10.1073/pnas.96.5.2104.