PMID- 17581980
OWN - NLM
STAT- MEDLINE
DCOM- 20070928
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 81
IP  - 17
DP  - 2007 Sep
TI  - Enterocyte proliferation and intestinal hyperplasia induced by simian virus 40 T 
      antigen require a functional J domain.
PG  - 9481-9
AB  - Transgenic mice expressing the simian virus 40 large T antigen (TAg) in 
      enterocytes develop intestinal hyperplasia that progresses to dysplasia with age. 
      This induction requires TAg action on the retinoblastoma (Rb) family of tumor 
      suppressors and is independent of the p53 pathway. In cell culture systems, the 
      inactivation of Rb proteins requires both a J domain in TAg that interacts with 
      hsc70 and an LXCXE motif that directs association with Rb proteins. Together 
      these elements are sufficient to release E2Fs from their association with Rb 
      family members. We have generated transgenic mice that express a J domain mutant 
      (D44N) in villus enterocytes. In contrast to wild-type TAg, the D44N mutant is 
      unable to induce enterocyte proliferation. Histological and morphological 
      examination revealed that mice expressing the J domain mutant have normal 
      intestines without loss of growth control. Unlike mice expressing wild-type TAg, 
      mice expressing D44N do not reduce the protein levels of p130 and are also unable 
      to dissociate p130-E2F DNA binding complexes. Furthermore, mice expressing D44N 
      in a null p130 background are still unable to develop hyperplasia. These studies 
      demonstrate that the ectopic proliferation of enterocytes by TAg requires a 
      functional J domain and suggest that the J domain is necessary to inactivate all 
      three pRb family members.
FAU - Rathi, Abhilasha V
AU  - Rathi AV
AD  - Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 
      15260, USA.
FAU - Saenz Robles, M Teresa
AU  - Saenz Robles MT
FAU - Pipas, James M
AU  - Pipas JM
LA  - eng
GR  - CA09895/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070620
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Animals
MH  - Antigens, Polyomavirus Transforming/chemistry/genetics/*physiology
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Enterocytes/cytology/*virology
MH  - Hyperplasia/*virology
MH  - Immunohistochemistry
MH  - Intestines/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation, Missense
MH  - Polyomavirus Infections/pathology
MH  - Protein Structure, Tertiary
MH  - Retinoblastoma Protein/metabolism
MH  - Simian virus 40/genetics/*physiology
MH  - Tumor Virus Infections/pathology
PMC - PMC1951414
EDAT- 2007/06/22 09:00
MHDA- 2007/09/29 09:00
PMCR- 2008/01/01
CRDT- 2007/06/22 09:00
PHST- 2007/06/22 09:00 [pubmed]
PHST- 2007/09/29 09:00 [medline]
PHST- 2007/06/22 09:00 [entrez]
PHST- 2008/01/01 00:00 [pmc-release]
AID - JVI.00922-07 [pii]
AID - 0922-07 [pii]
AID - 10.1128/JVI.00922-07 [doi]
PST - ppublish
SO  - J Virol. 2007 Sep;81(17):9481-9. doi: 10.1128/JVI.00922-07. Epub 2007 Jun 20.