PMID- 21346186
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20211020
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 22
IP  - 8
DP  - 2011 Apr 15
TI  - Gfer inhibits Jab1-mediated degradation of p27kip1 to restrict proliferation of 
      hematopoietic stem cells.
PG  - 1312-20
LID - 10.1091/mbc.E10-08-0723 [doi]
AB  - Growth factor erv1-like (Gfer) is an evolutionarily conserved sulfhydryl oxidase 
      that is enriched in embryonic and adult stem cells and plays an essential 
      prosurvival role in pluripotent embryonic stem cells. Here we show that knockdown 
      (KD) of Gfer in hematopoietic stem cells (HSCs) compromises their in vivo 
      engraftment potential and triggers a hyper-proliferative response that leads to 
      their exhaustion. KD of Gfer in HSCs does not elicit a significant alteration of 
      mitochondrial morphology or loss of cell viability. However, these cells possess 
      significantly reduced levels of the cyclin-dependent kinase inhibitor p27(kip1). 
      In contrast, overexpression of Gfer in HSCs results in significantly elevated 
      total and nuclear p27(kip1). KD of Gfer results in enhanced binding of p27(kip1) 
      to its inhibitor, the COP9 signalosome subunit jun activation-domain binding 
      protein 1 (Jab1), leading to its down-regulation. Conversely, overexpression of 
      Gfer results in its enhanced binding to Jab1 and inhibition of the Jab1-p27(kip1) 
      interaction. Furthermore, normalization of p27(kip1) in Gfer-KD HSCs rescues 
      their in vitro proliferation deficits. Taken together, our data demonstrate the 
      presence of a novel Gfer-Jab1-p27(kip1) pathway in HSCs that functions to 
      restrict abnormal proliferation.
FAU - Teng, Ellen C
AU  - Teng EC
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, NC 27707, USA.
FAU - Todd, Lance R
AU  - Todd LR
FAU - Ribar, Thomas J
AU  - Ribar TJ
FAU - Lento, William
AU  - Lento W
FAU - Dimascio, Leah
AU  - Dimascio L
FAU - Means, Anthony R
AU  - Means AR
FAU - Sankar, Uma
AU  - Sankar U
LA  - eng
GR  - R01 DK074701/DK/NIDDK NIH HHS/United States
GR  - DK 074701/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110223
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors)
RN  - EC 1.8.3.- (GFER protein, mouse)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.-.- (Cops5 protein, mouse)
RN  - EC 3.4.19.12 (COP9 Signalosome Complex)
SB  - IM
MH  - Animals
MH  - COP9 Signalosome Complex
MH  - *Cell Proliferation
MH  - Cell Survival/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p27/genetics/*metabolism
MH  - Down-Regulation
MH  - Gene Expression
MH  - Gene Expression Regulation, Developmental
MH  - Gene Knockdown Techniques
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/cytology/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Lentivirus
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Oxidoreductases Acting on Sulfur Group Donors/genetics/*metabolism
MH  - Peptide Hydrolases/genetics/*metabolism
MH  - Pluripotent Stem Cells/cytology/metabolism
MH  - Protein Binding/genetics
MH  - RNA, Small Interfering/metabolism
MH  - Recombinant Fusion Proteins/genetics/*metabolism
MH  - Transfection
MH  - Whole-Body Irradiation
PMC - PMC3078070
EDAT- 2011/02/25 06:00
MHDA- 2011/08/17 06:00
PMCR- 2011/06/30
CRDT- 2011/02/25 06:00
PHST- 2011/02/25 06:00 [entrez]
PHST- 2011/02/25 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
PHST- 2011/06/30 00:00 [pmc-release]
AID - mbc.E10-08-0723 [pii]
AID - E10-08-0723 [pii]
AID - 10.1091/mbc.E10-08-0723 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2011 Apr 15;22(8):1312-20. doi: 10.1091/mbc.E10-08-0723. Epub 2011 
      Feb 23.