PMID- 10764764
OWN - NLM
STAT- MEDLINE
DCOM- 20000720
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 24
DP  - 2000 Jun 16
TI  - NF-Y and Sp1 cooperate for the transcriptional activation and cAMP response of 
      human tissue inhibitor of metalloproteinases-2.
PG  - 18602-10
AB  - The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of 
      MMPs (TIMPs) is a key determinant in the homeostasis of the extracellular matrix. 
      We have identified two cis-acting elements involved in the transcriptional 
      regulation of TIMP-2. The first is an inverted CCAAT box located at position -73 
      to -69 in the TIMP-2 promoter that binds the transcription factor NF-Y. The 
      second is a GAGGAGGGGG motif located at position -107 to -98, that binds the 
      transcription factors Sp1 and Sp3. NF-Y and Sp1 cooperate for the basal 
      transcription activity of the promoter. We then determined that TIMP-2 is 
      transcriptionally up-regulated by cAMP analogs. Up-regulation of TIMP-2 by 
      dibutyryl cAMP is a delayed response that requires de novo protein synthesis and 
      does not affect RNA stability. The NF-Y and the Sp1 binding site are both 
      involved in cAMP-dependent up-regulation of TIMP-2. Whereas NF-Y is essential for 
      cAMP mediated regulation, Sp1 alone is not sufficient but enhances the activity 
      of NF-Y. Dibutyryl cAMP has no effect on the expression of MMP-2 and MMP-9 and 
      switches the MMP-TIMP balance in favor of the inhibitor.
FAU - Zhong, Z D
AU  - Zhong ZD
AD  - Division of Hematology-Oncology, Department of Pediatrics, Children's Hospital 
      Los Angeles, Keck School of Medicine, University of Southern California, Los 
      Angeles, California 90027, USA.
FAU - Hammani, K
AU  - Hammani K
FAU - Bae, W S
AU  - Bae WS
FAU - DeClerck, Y A
AU  - DeClerck YA
LA  - eng
GR  - CA 42919/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Sp1 Transcription Factor)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Cyclic AMP/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Humans
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Promoter Regions, Genetic
MH  - Sp1 Transcription Factor/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics/*metabolism
MH  - *Transcriptional Activation
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2000/04/15 09:00
MHDA- 2000/07/25 11:00
CRDT- 2000/04/15 09:00
PHST- 2000/04/15 09:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/04/15 09:00 [entrez]
AID - S0021-9258(19)83226-X [pii]
AID - 10.1074/jbc.M001389200 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jun 16;275(24):18602-10. doi: 10.1074/jbc.M001389200.