PMID- 10330192
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 6
DP  - 1999 Jun
TI  - Identification of CHIP, a novel tetratricopeptide repeat-containing protein that 
      interacts with heat shock proteins and negatively regulates chaperone functions.
PG  - 4535-45
AB  - The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and
      Hsp70 is modulated by physical interactions with four previously identified
      chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the
      Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a
      tetratricopeptide repeat domain. In a search for additional tetratricopeptide
      repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic
      protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly
      expressed in adult striated muscle in vivo and is expressed broadly in vitro in
      tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners
      for this protein in a yeast two-hybrid screen. In vitro binding assays
      demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and
      complexes containing CHIP and Hsc70 were identified in immunoprecipitates of
      human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we 
      found that CHIP interacted with the carboxy-terminal residues 540 to 650 of
      Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197
      (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP.
      Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70,
      suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70
      substrate-binding cycle. Consistent with this observation, both luciferase
      refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited
      by CHIP. Taken together, these results indicate that CHIP decreases net ATPase
      activity and reduces chaperone efficiency, and they implicate CHIP in the
      negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding 
      cycle.
FAU - Ballinger, C A
AU  - Ballinger CA
AD  - University of Texas Medical Branch, Division of Cardiology and Sealy Center for
      Molecular Cardiology, Galveston, Texas, USA.
FAU - Connell, P
AU  - Connell P
FAU - Wu, Y
AU  - Wu Y
FAU - Hu, Z
AU  - Hu Z
FAU - Thompson, L J
AU  - Thompson LJ
FAU - Yin, L Y
AU  - Yin LY
FAU - Patterson, C
AU  - Patterson C
LA  - eng
SI  - GENBANK/AF129084
SI  - GENBANK/AF129085
SI  - GENBANK/AF129086
GR  - AG15234/AG/NIA NIH HHS/United States
GR  - HL03658/HL/NHLBI 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  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Carrier Proteins)
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (HSPA8 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hspa8 protein, mouse)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.3.2.27 (STUB1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.8.1.1 (Thiosulfate Sulfurtransferase)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Adenosine Triphosphatases/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Brain/metabolism
MH  - COS Cells
MH  - Carrier Proteins/*genetics/metabolism/*physiology
MH  - Cloning, Molecular
MH  - Drosophila/genetics
MH  - Gene Library
MH  - HSC70 Heat-Shock Proteins
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - HeLa Cells
MH  - Heat-Shock Proteins/*physiology
MH  - Humans
MH  - Immunoblotting
MH  - *Ligases
MH  - Luciferases/metabolism
MH  - Mice
MH  - Models, Biological
MH  - Molecular Chaperones/*physiology
MH  - Molecular Sequence Data
MH  - Muscle, Skeletal/metabolism
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Biosynthesis
MH  - Recombinant Fusion Proteins
MH  - Sequence Homology, Amino Acid
MH  - Thiosulfate Sulfurtransferase/metabolism
MH  - Time Factors
MH  - Tissue Distribution
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - U937 Cells
MH  - *Ubiquitin-Protein Ligases
PMC - PMC104411
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1128/mcb.19.6.4535 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jun;19(6):4535-45. doi: 10.1128/mcb.19.6.4535.