PMID- 12566432
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20181113
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 160
IP  - 3
DP  - 2003 Feb 3
TI  - The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation 
      and cell density.
PG  - 423-32
AB  - Epithelial tight junctions regulate paracellular permeability, restrict 
      apical/basolateral intramembrane diffusion of lipids, and have been proposed to 
      participate in the control of epithelial cell proliferation and differentiation. 
      Previously, we have identified ZO-1-associated nucleic acid binding proteins 
      (ZONAB), a Y-box transcription factor whose nuclear localization and 
      transcriptional activity is regulated by the tight junction-associated candidate 
      tumor suppressor ZO-1. Now, we found that reduction of ZONAB expression using an 
      antisense approach or by RNA interference strongly reduced proliferation of MDCK 
      cells. Transfection of wild-type or ZONAB-binding fragments of ZO-1 reduced 
      proliferation as well as nuclear ZONAB pools, indicating that promotion of 
      proliferation by ZONAB requires its nuclear accumulation. Overexpression of ZONAB 
      resulted in increased cell density in mature monolayers, and depletion of ZONAB 
      or overexpression of ZO-1 reduced cell density. ZONAB was found to associate with 
      cell division kinase (CDK) 4, and reduction of nuclear ZONAB levels resulted in 
      reduced nuclear CDK4. Thus, our data indicate that tight junctions can regulate 
      epithelial cell proliferation and cell density via a ZONAB/ZO-1-based pathway. 
      Although this regulatory process may also involve regulation of transcription by 
      ZONAB, our data suggest that one mechanism by which ZONAB and ZO-1 influence 
      proliferation is by regulating the nuclear accumulation of CDK4.
FAU - Balda, Maria S
AU  - Balda MS
AD  - Division of Cell Biology, Institute of Ophthalmology, University College London, 
      London EC1V 9EL, UK. m.balda@ucl.ac.uk
FAU - Garrett, Michelle D
AU  - Garrett MD
FAU - Matter, Karl
AU  - Matter K
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Antisense)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TJP1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (ZONAB protein, Canis familiaris)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/physiology
MH  - Animals
MH  - Cell Communication/*physiology
MH  - Cell Division/*physiology
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism
MH  - Cyclin-Dependent Kinases/metabolism
MH  - DNA-Binding Proteins/*deficiency/genetics
MH  - Epithelial Cells/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - Protein Structure, Tertiary/physiology
MH  - *Proto-Oncogene Proteins
MH  - RNA, Antisense/genetics
MH  - Recombinant Fusion Proteins
MH  - Signal Transduction/physiology
MH  - Tight Junctions/*metabolism
MH  - Transcription Factors/*deficiency/genetics
MH  - Zonula Occludens-1 Protein
PMC - PMC2172662
EDAT- 2003/02/05 04:00
MHDA- 2003/03/13 04:00
PMCR- 2003/08/03
CRDT- 2003/02/05 04:00
PHST- 2003/02/05 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2003/02/05 04:00 [entrez]
PHST- 2003/08/03 00:00 [pmc-release]
AID - jcb.200210020 [pii]
AID - 200210020 [pii]
AID - 10.1083/jcb.200210020 [doi]
PST - ppublish
SO  - J Cell Biol. 2003 Feb 3;160(3):423-32. doi: 10.1083/jcb.200210020.