PMID- 20178741
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20211203
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 140
IP  - 4
DP  - 2010 Feb 19
TI  - Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase 
      CRL4(DCAF1) in the nucleus.
PG  - 477-90
LID - 10.1016/j.cell.2010.01.029 [doi]
AB  - Current models imply that the FERM domain protein Merlin, encoded by the tumor 
      suppressor NF2, inhibits mitogenic signaling at or near the plasma membrane. 
      Here, we show that the closed, growth-inhibitory form of Merlin accumulates in 
      the nucleus, binds to the E3 ubiquitin ligase CRL4(DCAF1), and suppresses its 
      activity. Depletion of DCAF1 blocks the promitogenic effect of inactivation of 
      Merlin. Conversely, enforced expression of a Merlin-insensitive mutant of DCAF1 
      counteracts the antimitogenic effect of Merlin. Re-expression of Merlin and 
      silencing of DCAF1 implement a similar, tumor-suppressive program of gene 
      expression. Tumor-derived mutations invariably disrupt Merlin's ability to 
      interact with or inhibit CRL4(DCAF1). Finally, depletion of DCAF1 inhibits the 
      hyperproliferation of Schwannoma cells from NF2 patients and suppresses the 
      oncogenic potential of Merlin-deficient tumor cell lines. We propose that Merlin 
      suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1).
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Li, Wei
AU  - Li W
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
FAU - You, Liru
AU  - You L
FAU - Cooper, Jonathan
AU  - Cooper J
FAU - Schiavon, Gaia
AU  - Schiavon G
FAU - Pepe-Caprio, Angela
AU  - Pepe-Caprio A
FAU - Zhou, Lu
AU  - Zhou L
FAU - Ishii, Ryohei
AU  - Ishii R
FAU - Giovannini, Marco
AU  - Giovannini M
FAU - Hanemann, C Oliver
AU  - Hanemann CO
FAU - Long, Stephen B
AU  - Long SB
FAU - Erdjument-Bromage, Hediye
AU  - Erdjument-Bromage H
FAU - Zhou, Pengbo
AU  - Zhou P
FAU - Tempst, Paul
AU  - Tempst P
FAU - Giancotti, Filippo G
AU  - Giancotti FG
LA  - eng
SI  - GEO/GSE19305
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P30 CA008748-44/CA/NCI NIH HHS/United States
GR  - R01 CA098210/CA/NCI NIH HHS/United States
GR  - P30 CA08748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Carrier Proteins)
RN  - 0 (Neurofibromin 2)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (DCAF1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Carrier Proteins/chemistry/*metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Mesothelioma/*metabolism
MH  - Models, Molecular
MH  - Neurilemmoma/*metabolism
MH  - Neurofibromin 2/*metabolism
MH  - Protein Serine-Threonine Kinases
MH  - Ubiquitin-Protein Ligases
PMC - PMC2828953
MID - NIHMS175286
EDAT- 2010/02/25 06:00
MHDA- 2010/03/24 06:00
PMCR- 2011/02/19
CRDT- 2010/02/25 06:00
PHST- 2009/01/22 00:00 [received]
PHST- 2009/08/07 00:00 [revised]
PHST- 2010/01/16 00:00 [accepted]
PHST- 2010/02/25 06:00 [entrez]
PHST- 2010/02/25 06:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
PHST- 2011/02/19 00:00 [pmc-release]
AID - S0092-8674(10)00064-4 [pii]
AID - 10.1016/j.cell.2010.01.029 [doi]
PST - ppublish
SO  - Cell. 2010 Feb 19;140(4):477-90. doi: 10.1016/j.cell.2010.01.029.