PMID- 20484573
OWN - NLM
STAT- MEDLINE
DCOM- 20101021
LR  - 20211020
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 21
IP  - 14
DP  - 2010 Jul 15
TI  - Lens fiber cell differentiation and denucleation are disrupted through expression 
      of the N-terminal nuclear receptor box of NCOA6 and result in p53-dependent and 
      p53-independent apoptosis.
PG  - 2453-68
AB  - Nuclear receptor coactivator 6 (NCOA6) is a multifunctional protein implicated in 
      embryonic development, cell survival, and homeostasis. An 81-amino acid fragment, 
      dnNCOA6, containing the N-terminal nuclear receptor box (LXXLL motif) of NCOA6, 
      acts as a dominant-negative (dn) inhibitor of NCOA6. Here, we expressed dnNCOA6 
      in postmitotic transgenic mouse lens fiber cells. The transgenic lenses showed 
      reduced growth; a wide spectrum of lens fiber cell differentiation defects, 
      including reduced expression of gamma-crystallins; and cataract formation. Those 
      lens fiber cells entered an alternate proapoptotic pathway, and the denucleation 
      (karyolysis) process was stalled. Activation of caspase-3 at embryonic day 
      (E)13.5 was followed by double-strand breaks (DSBs) formation monitored via a 
      biomarker, gamma-H2AX. Intense terminal deoxynucleotidyl transferase dUTP 
      nick-end labeling (TUNEL) signals were found at E16.5. Thus, a window of 
      approximately 72 h between these events suggested prolonged though incomplete 
      apoptosis in the lens fiber cell compartment that preserved nuclei in its cells. 
      Genetic experiments showed that the apoptotic-like processes in the transgenic 
      lens were both p53-dependent and p53-independent. Lens-specific deletion of Ncoa6 
      also resulted in disrupted lens fiber cell differentiation. Our data demonstrate 
      a cell-autonomous role of Ncoa6 in lens fiber cell differentiation and suggest 
      novel insights into the process of lens fiber cell denucleation and apoptosis.
FAU - Wang, Wei-Lin
AU  - Wang WL
AD  - Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, 
      USA.
FAU - Li, Qingtian
AU  - Li Q
FAU - Xu, Jianming
AU  - Xu J
FAU - Cvekl, Ales
AU  - Cvekl A
LA  - eng
GR  - R01 EY012200/EY/NEI NIH HHS/United States
GR  - EY-014237/EY/NEI NIH HHS/United States
GR  - R01EY-012200/EY/NEI NIH HHS/United States
GR  - R01 EY014237/EY/NEI NIH HHS/United States
GR  - R01 CA119689/CA/NCI NIH HHS/United States
GR  - CA-119689/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100519
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Ncoa6 protein, mouse)
RN  - 0 (Nuclear Receptor Coactivators)
RN  - 0 (Proto-Oncogene Proteins c-maf)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (gamma-Crystallins)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Amino Acid Motifs
MH  - Animals
MH  - *Apoptosis
MH  - Caspase 3/metabolism
MH  - Cataract/complications/pathology
MH  - *Cell Differentiation
MH  - Enzyme Activation
MH  - Gene Deletion
MH  - In Situ Nick-End Labeling
MH  - Lens, Crystalline/abnormalities/metabolism/*pathology/ultrastructure
MH  - Mice
MH  - Mice, Transgenic
MH  - Microphthalmos/complications/pathology
MH  - Models, Biological
MH  - Nuclear Receptor Coactivators/*chemistry/*metabolism
MH  - Organ Specificity
MH  - Proto-Oncogene Proteins c-maf/metabolism
MH  - Structure-Activity Relationship
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - gamma-Crystallins/metabolism
PMC - PMC2903674
EDAT- 2010/05/21 06:00
MHDA- 2010/10/22 06:00
PMCR- 2010/09/30
CRDT- 2010/05/21 06:00
PHST- 2010/05/21 06:00 [entrez]
PHST- 2010/05/21 06:00 [pubmed]
PHST- 2010/10/22 06:00 [medline]
PHST- 2010/09/30 00:00 [pmc-release]
AID - E09-12-1031 [pii]
AID - 3607891 [pii]
AID - 10.1091/mbc.e09-12-1031 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2010 Jul 15;21(14):2453-68. doi: 10.1091/mbc.e09-12-1031. Epub 
      2010 May 19.