scholarly journals The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family.

1996 ◽  
Vol 271 (5) ◽  
pp. 2874
Author(s):  
Suneel S. Apte ◽  
Bjorn R. Olsen ◽  
Gillian Murphy
Keyword(s):  
Gene Family ◽  
Gene Structure ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Inhibitory Activities ◽  
Timp Gene

Expression of the tissue inhibitor of metalloproteinases (TIMP) gene family in normal and osteoarthritic joints

1999 ◽  
Vol 18 (5-6) ◽  
pp. 183-191 ◽  
Author(s):  
S. Su ◽  
J. Grover ◽  
P. J. Roughley ◽  
J. A. DiBattista ◽  
J. Martel-Pelletier ◽  
...  
Keyword(s):  
Gene Family ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Timp Gene

scholarly journals The purification of tissue inhibitor of metalloproteinases-2 from its 72 kDa progelatinase complex. Demonstration of the biochemical similarities of tissue inhibitor of metalloproteinases-2 and tissue inhibitor of metalloproteinases-1

1991 ◽  
Vol 278 (1) ◽  
pp. 179-187 ◽  
Author(s):  
R V Ward ◽  
R M Hembry ◽  
J J Reynolds ◽  
G Murphy
Keyword(s):  
Molecular Mass ◽  
Polyclonal Antiserum ◽  
High Molecular Mass ◽  
U937 Cells ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Gingival Fibroblasts ◽  
Tissue Inhibitor ◽  
Lower Molecular Mass ◽  
Inhibitory Activities

Human gingival fibroblasts in culture were shown to secrete a 72 kDa progelatinase, of which a proportion in the medium was found to be complexed with tissue inhibitor of metalloproteinases-2 (TIMP-2). A purification procedure was devised to purify free enzyme and inhibitor. We also describe the purification of both 95 kDa progelatinase bound to TIMP-1 and free 95 kDa progelatinase from the medium of U937 cells. A polyclonal antiserum to TIMP-2 was prepared and it was shown that TIMP-1 and TIMP-2 are antigenically distinct. The ability to form stable complexes and the relative inhibitory activities of TIMP-1 and TIMP-2 towards 95 kDa and 72 kDa gelatinases, collagenase, stromelysins 1 and 2 and punctuated metalloproteinase were determined; only minor differences were found. Complex-formation between TIMP-2 and 72 kDa progelatinase was demonstrated not to reduce the metalloproteinase-inhibitory activity of TIMP-2, a finding that led to the characterization of high-molecular-mass TIMP activity. Competition experiments between progelatinases and active gelatinases for TIMPs indicated that the affinity of TIMPs for progelatinases is weaker than that for active gelatinases. In a study of the effects of TIMP-1 and TIMP-2 on progelatinase self-cleavage we found that both TIMP-1 and TIMP-2 inhibit the conversion of 95 kDa and 72 kDa progelatinases and prostromelysin into lower-molecular-mass forms. TIMP capable of complexing with progelatinase was shown to be no more efficient an inhibitor of gelatinase self-cleavage than TIMP not able to complex with progelatinase.

scholarly journals Increased erythroid potentiating activity/tissue inhibitor of metalloproteinases and jun/fos transcription factor complex characterize tumor promoter-induced megakaryoblastic differentiation of K562 leukemia cells

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1974-1982 ◽  
Author(s):  
R Alitalo ◽  
J Partanen ◽  
L Pertovaara ◽  
E Holtta ◽  
L Sistonen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Northern Hybridization ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Fold Induction ◽  
Transcription Factor Complex ◽  
Timp Gene

Abstract Molecular cloning has revealed that erythroid potentiating activity (EPA) and tissue inhibitor of metalloproteinases (TIMP) represent two distinct activities of a single protein. We have studied the expression of the EPA/TIMP gene at the mRNA and protein levels during 12-O- tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryoblastic differentiation of K562 human chronic myeloid leukemia cells. Northern hybridization analysis showed that the EPA/TIMP mRNA was increased within 3 hours of TPA-induction and reached maximal levels (about 50- fold induction) during the first day of treatment. The expression of mRNAs for two major metalloproteinases, collagenase-I and stromelysin, were activated in parallel in the differentiation-induced K562 cells. The increase of EPA/TIMP mRNA correlated with increased EPA/TIMP protein biosynthesis and secretion: the TPA-induced cells secreted substantially enhanced amounts of metabolically labeled proteins, of which EPA/TIMP represented up to 50% after the first day of treatment (over 100-fold induction). The induction of EPA/TIMP mRNA was associated with its increased transcription. EPA/TIMP induction required continuous protein synthesis, being completely inhibited by addition of the protein synthesis inhibitor cycloheximide simultaneously with TPA, but only partially inhibited in a time- dependent manner if cycloheximide was added after TPA. Unlike in other cells tested, the jun and c-fos transcription factor mRNAs showed a prolonged biphasic induction response in K562 cells during TPA treatment. This response was associated with enhanced activity of a transfected recombinant reporter plasmid containing binding sites for the jun/fos transcription factor complex (AP-1) similar to the TPA- responsive element (TRE) sequence we found in the EPA/TIMP gene promoter. We suggest that the induction of EPA/TIMP and several other genes specific for the differentiating K562 cells may be a consequence of the sustained activation of immediate early genes encoding transcription factors, such as jun and c-fos.

scholarly journals The prognostic and diagnostic value of tissue inhibitor of metalloproteinases gene family and potential function in gastric cancer

2021 ◽  
Vol 12 (13) ◽  
pp. 4086-4098
Author(s):  
Zhao Li ◽  
Qinwen Jing ◽  
Liucheng Wu ◽  
Jiansi Chen ◽  
Mingwei Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gene Family ◽  
Potential Function ◽  
Diagnostic Value ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor

scholarly journals Increased erythroid potentiating activity/tissue inhibitor of metalloproteinases and jun/fos transcription factor complex characterize tumor promoter-induced megakaryoblastic differentiation of K562 leukemia cells

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1974-1982 ◽  
Author(s):  
R Alitalo ◽  
J Partanen ◽  
L Pertovaara ◽  
E Holtta ◽  
L Sistonen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Northern Hybridization ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Fold Induction ◽  
Transcription Factor Complex ◽  
Timp Gene

Molecular cloning has revealed that erythroid potentiating activity (EPA) and tissue inhibitor of metalloproteinases (TIMP) represent two distinct activities of a single protein. We have studied the expression of the EPA/TIMP gene at the mRNA and protein levels during 12-O- tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryoblastic differentiation of K562 human chronic myeloid leukemia cells. Northern hybridization analysis showed that the EPA/TIMP mRNA was increased within 3 hours of TPA-induction and reached maximal levels (about 50- fold induction) during the first day of treatment. The expression of mRNAs for two major metalloproteinases, collagenase-I and stromelysin, were activated in parallel in the differentiation-induced K562 cells. The increase of EPA/TIMP mRNA correlated with increased EPA/TIMP protein biosynthesis and secretion: the TPA-induced cells secreted substantially enhanced amounts of metabolically labeled proteins, of which EPA/TIMP represented up to 50% after the first day of treatment (over 100-fold induction). The induction of EPA/TIMP mRNA was associated with its increased transcription. EPA/TIMP induction required continuous protein synthesis, being completely inhibited by addition of the protein synthesis inhibitor cycloheximide simultaneously with TPA, but only partially inhibited in a time- dependent manner if cycloheximide was added after TPA. Unlike in other cells tested, the jun and c-fos transcription factor mRNAs showed a prolonged biphasic induction response in K562 cells during TPA treatment. This response was associated with enhanced activity of a transfected recombinant reporter plasmid containing binding sites for the jun/fos transcription factor complex (AP-1) similar to the TPA- responsive element (TRE) sequence we found in the EPA/TIMP gene promoter. We suggest that the induction of EPA/TIMP and several other genes specific for the differentiating K562 cells may be a consequence of the sustained activation of immediate early genes encoding transcription factors, such as jun and c-fos.

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