PMID- 10635329
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20191210
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 4
IP  - 6
DP  - 1999 Dec
TI  - Formation of the VHL-elongin BC tumor suppressor complex is mediated by the
      chaperonin TRiC.
PG  - 1051-61
AB  - von Hippel-Lindau (VHL) disease is caused by loss of function of the VHL tumor
      suppressor protein. Here, we demonstrate that the folding and assembly of VHL
      into a complex with its partner proteins, elongin B and elongin C (herein,
      elongin BC), is directly mediated by the chaperonin TRiC/CCT. Association of VHL 
      with TRiC is required for formation of the VHL-elongin BC complex. A 55-amino
      acid domain of VHL is both necessary and sufficient for binding to TRiC.
      Importantly, mutation or deletion of this domain is associated with VHL disease. 
      We identified two mutations that disrupt the normal interaction with TRiC and
      impair VHL folding. Our results define a novel role for TRiC in mediating
      oligomerization and suggest that inactivating mutations can impair polypeptide
      function by interfering with chaperone-mediated folding.
FAU - Feldman, D E
AU  - Feldman DE
AD  - Department of Biological Sciences, Stanford University, California 94305, USA.
FAU - Thulasiraman, V
AU  - Thulasiraman V
FAU - Ferreyra, R G
AU  - Ferreyra RG
FAU - Frydman, J
AU  - Frydman J
LA  - eng
GR  - GM56433/GM/NIGMS 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
JT  - Molecular cell
JID - 9802571
RN  - 0 (ELOB protein, human)
RN  - 0 (ELOC protein, human)
RN  - 0 (Elongin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.3.2.27 (PPP1R11 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - EC 3.6.1.- (Chaperonins)
RN  - EC 6.- (Ligases)
RN  - EC 6.3.2.- (VHL protein, human)
SB  - IM
MH  - Chaperonins/genetics
MH  - Elongin
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - *Ligases
MH  - *Microtubule-Associated Proteins
MH  - Mutation
MH  - Nuclear Proteins/*genetics/metabolism
MH  - Protein Folding
MH  - Proteins/chemistry/*genetics/metabolism
MH  - Transcription Factors/*genetics/metabolism
MH  - *Tumor Suppressor Proteins
MH  - *Ubiquitin-Protein Ligases
MH  - Von Hippel-Lindau Tumor Suppressor Protein
MH  - t-Complex Genome Region
MH  - von Hippel-Lindau Disease/*genetics
EDAT- 2000/01/15 00:00
MHDA- 2000/01/15 00:01
CRDT- 2000/01/15 00:00
PHST- 2000/01/15 00:00 [pubmed]
PHST- 2000/01/15 00:01 [medline]
PHST- 2000/01/15 00:00 [entrez]
AID - S1097-2765(00)80233-6 [pii]
AID - 10.1016/s1097-2765(00)80233-6 [doi]
PST - ppublish
SO  - Mol Cell. 1999 Dec;4(6):1051-61. doi: 10.1016/s1097-2765(00)80233-6.