PMID- 1641004
OWN - NLM
STAT- MEDLINE
DCOM- 19920828
LR  - 20100204
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 358
IP  - 6384
DP  - 1992 Jul 23
TI  - Retinoblastoma gene product activates expression of the human TGF-beta 2 gene 
      through transcription factor ATF-2.
PG  - 331-4
AB  - The retinoblastoma susceptibility gene product (pRb) plays an important role in 
      constraining cellular proliferation and in regulating the cell cycle. The pRb 
      inhibits transcription of genes involved in growth control (reviewed in ref. 3) 
      and can regulate transforming growth factor beta 1 (TGF-beta 1) gene expression. 
      TGF-beta isoforms also down-regulate cellular proliferation. To determine whether 
      pRb also regulates expression of other TGF-beta isoforms, we examined the effect 
      of pRb on the expression of the human TGF-beta 2 gene. The human TGF-beta 2 
      promoter contains multiple elements including an ATF site, which is essential for 
      basal promoter activity. Here we report that pRb activates transcription of the 
      human TGF-beta 2 gene. The promoter element responsible for pRb-mediated 
      transcriptional regulation is a binding site for ATF proteins, an extensive 
      transcription factor family. We provide evidence that implicates ATF-2 in 
      pRb-responsiveness. First, the ATF promoter element in the TGF-beta 2 gene is a 
      high-affinity ATF-2-binding site. Second, a GAL4-ATF2 fusion protein can support 
      pRb-mediated transcriptional activation of a promoter containing GAL4-binding 
      sites. Third, ATF-2 in nuclear extracts can interact with pRb. Our results reveal 
      a new mechanism by which pRb constrains cellular proliferation: by activating 
      expression of the inhibitory growth factor, TGF-beta 2.
FAU - Kim, S J
AU  - Kim SJ
AD  - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 
      20892.
FAU - Wagner, S
AU  - Wagner S
FAU - Liu, F
AU  - Liu F
FAU - O'Reilly, M A
AU  - O'Reilly MA
FAU - Robbins, P D
AU  - Robbins PD
FAU - Green, M R
AU  - Green MR
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (ATF2 protein, human)
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Activating Transcription Factors)
RN  - 0 (Blood Proteins)
RN  - 0 (Immune Sera)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Activating Transcription Factor 2
MH  - Activating Transcription Factors
MH  - Base Sequence
MH  - Blood Proteins/immunology/*metabolism
MH  - Cell Line
MH  - Chloramphenicol O-Acetyltransferase/genetics/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Genes, Retinoblastoma
MH  - HeLa Cells
MH  - Humans
MH  - Immune Sera
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins
MH  - Oligodeoxyribonucleotides
MH  - Plasmids
MH  - Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Retinoblastoma Protein/*metabolism
MH  - Transcription Factors/immunology/*metabolism
MH  - Transfection
MH  - Transforming Growth Factor beta/*genetics
EDAT- 1992/07/23 00:00
MHDA- 1992/07/23 00:01
CRDT- 1992/07/23 00:00
PHST- 1992/07/23 00:00 [pubmed]
PHST- 1992/07/23 00:01 [medline]
PHST- 1992/07/23 00:00 [entrez]
AID - 10.1038/358331a0 [doi]
PST - ppublish
SO  - Nature. 1992 Jul 23;358(6384):331-4. doi: 10.1038/358331a0.