Abstract:
:Matrix metalloproteinases (MMPs) exert both pro- and antiangiogenic functions by the release of cytokines or proteolytically generated angiogenic inhibitors from extracellular matrix and basement membrane remodeling. In the Mmp2-/- mouse neovascularization is greatly reduced, but the mechanistic aspects of this remain unclear. Using isotope-coded affinity tag labeling of proteins analyzed by multidimensional liquid chromatography and tandem mass spectrometry we explored proteome differences between Mmp2-/- cells and those rescued by MMP-2 transfection. Proteome signatures that are hallmarks of proteolysis revealed cleavage of many known MMP-2 substrates in the cellular context. Proteomic evidence of MMP-2 processing of novel substrates was found. Insulin-like growth factor binding protein 6, follistatin-like 1, and cystatin C protein cleavage by MMP-2 was biochemically confirmed, and the cleavage sites in heparin affin regulatory peptide (HARP; pleiotrophin) and connective tissue growth factor (CTGF) were sequenced by matrix-assisted laser desorption ionization-time of flight mass spectrometry. MMP-2 processing of HARP and CTGF released vascular endothelial growth factor (VEGF) from angiogenic inhibitory complexes. The cleaved HARP N-terminal domain increased HARP-induced cell proliferation, whereas the HARP C-terminal domain was antagonistic and decreased cell proliferation and migration. Hence the unmasking of cytokines, such as VEGF, by metalloproteinase processing of their binding proteins is a new mechanism in the control of cytokine activation and angiogenesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Dean RA,Butler GS,Hamma-Kourbali Y,Delbé J,Brigstock DR,Courty J,Overall CMdoi
10.1128/MCB.00821-07subject
Has Abstractpub_date
2007-12-01 00:00:00pages
8454-65issue
24eissn
0270-7306issn
1098-5549pii
MCB.00821-07journal_volume
27pub_type
杂志文章abstract::The accumulation of assembled holoenzymes composed of regulatory D-type cyclins and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting for progression through the G1 phase of the cell cycle in mammalian fibroblasts. Both the synthesis and assembly of D-type cyclins and cdk4 depend upon serum s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.4.2713
更新日期:1994-04-01 00:00:00
abstract::As part of an effort to characterize the spatial and functional relationships among genetic elements within the amplified dihydrofolate reductase (DHFR) domain in Chinese hamster cells, we have used a variation of the differential hybridization approach to identify cDNA clones whose genes are coamplified with DHFR in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.3.1137
更新日期:1989-03-01 00:00:00
abstract::Heteroduplexes were prepared from two plasmids, pRH4-14/TK and pRH5-8/TK, containing different amber mutations in the neomycin resistance gene (Neor). The Neor gene was engineered to be expressed in both bacterial and mammalian cells. A functional Neor gene conferred kanamycin resistance to bacteria and resistance to ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.1.70
更新日期:1985-01-01 00:00:00
abstract::The E2F1, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes. Here we use mutant mouse strains to investigate E2F3's role in vivo. We show that E2F3 is essential for embryonic viability in the pure 129...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.8.2663-2672.2002
更新日期:2002-04-01 00:00:00
abstract::The female-sterile ovarian tumor gene, otu, is located in cytological region 7F1 on the Drosophila melanogaster chromosome map. We have mapped the gene at the molecular level by using four dysgenic alleles and two revertant derivatives of these alleles as well as an ethyl methanesulfonate-induced allele. The insertion...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1481
更新日期:1988-04-01 00:00:00
abstract::The mRNA for transforming growth factor beta 3 (TGF-beta 3) includes a long (1.1-kb) 5' noncoding region which exerts a potent inhibitory effect on translational efficiency. We now report that many human breast cancer cell lines (T47-D, SK-BR-3, ZR-75-1, and BT-474) express two mRNA species for TGF-beta 3: the 3.5-kb ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.619
更新日期:1994-01-01 00:00:00
abstract::Expression of the anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 is required for the accumulation of APC/C substrates crucial for DNA synthesis and mitotic entry. We show that in vivo Emi1 expression correlates with the proliferative status of the cellular compartment and that cells lacking Emi1 undergo c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00908-07
更新日期:2007-11-01 00:00:00
abstract::Heterogeneous nuclear RNA contains double-stranded regions that are not found in mRNA and that may serve as recognition elements for processing enzymes. The double-stranded regions of heterogeneous nuclear RNA prepared from HeLa cells promoted the synthesis of (2',5')oligoadenylate [(2',5')oligo(A) or (2'5')An] when i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.2.154
更新日期:1982-02-01 00:00:00
abstract::The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-gamma (PLC-gamma); and is thought to be important for interleukin-2 gene transcription in T cells. To define the role of 3BP2 in lymphocyte development and function, we generated 3BP2-deficient mice. T-cell development,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00087-06
更新日期:2006-07-01 00:00:00
abstract::To investigate the role of insulin receptor substrate 1 (IRS-1) and IRS-2, the two ubiquitously expressed IRS proteins, in adipocyte differentiation, we established embryonic fibroblast cells with four different genotypes, i.e., wild-type, IRS-1 deficient (IRS-1(-/-)), IRS-2 deficient (IRS-2(-/-)), and IRS-1 IRS-2 dou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.7.2521-2532.2001
更新日期:2001-04-01 00:00:00
abstract::We evaluated the extent to which muscle-specific genes display identical patterns of mRNA accumulation during human myogenesis. Cloned satellite cells isolated from adult human skeletal muscle were expanded in culture, and RNA was isolated from low- and high-confluence cells and from fusing cultures over a 15-day time...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.11.4100
更新日期:1987-11-01 00:00:00
abstract::mRNAs are monitored for errors in gene expression by RNA surveillance, in which mRNAs that cannot be fully translated are degraded by the nonsense-mediated mRNA decay pathway (NMD). RNA surveillance ensures that potentially deleterious truncated proteins are seldom made. NMD pathways that promote surveillance have bee...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6710
更新日期:1999-10-01 00:00:00
abstract::Glucose and oxygen are two of the most important molecules transferred from mother to fetus during eutherian pregnancy, and the metabolic fates of these nutrients converge at the transport and metabolism of pyruvate in mitochondria. Pyruvate enters the mitochondrial matrix through the mitochondrial pyruvate carrier (M...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00166-16
更新日期:2016-07-14 00:00:00
abstract::Regulation of chromatin through histone acetylation is an important step in gene expression. The Gcn5 histone acetyltransferase is part of protein complexes, e.g., the SAGA complex, that interact with transcriptional activators, targeting the enzyme to specific promoters and assisting in recruitment of the basal RNA p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.18.8080-8089.2004
更新日期:2004-09-01 00:00:00
abstract::2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17beta-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent deg...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.6.1843-1855.2003
更新日期:2003-03-01 00:00:00
abstract::The TIS11 primary response gene is rapidly and transiently induced by both 12-O-tetradecanoylphorbol-13-acetate and growth factors. The predicted TIS11 protein contains a 6-amino-acid repeat, YKTELC. We cloned two additional cDNAs, TIS11b and TIS11d, that contain the YKTELC sequence. TIS11, TIS11b, and TIS11d proteins...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1754
更新日期:1991-03-01 00:00:00
abstract::The Msh2-Msh3 heterodimer recognizes various DNA mispairs, including loops of DNA ranging from 1 to 14 nucleotides and some base-base mispairs. Homology modeling of the mispair-binding domain (MBD) of Msh3 using the related Msh6 MBD revealed that mismatch recognition must be different, even though the MBD folds must b...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01558-09
更新日期:2010-07-01 00:00:00
abstract::The cys-3+ gene of Neurospora crassa encodes a bZIP (basic region-leucine zipper) regulatory protein that is essential for sulfur structural gene expression (e.g., ars-1+). Nuclear transcription assays confirmed that cys-3+ was under sulfur-regulated transcriptional control and that cys-3+ transcription was constituti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.4.1568
更新日期:1992-04-01 00:00:00
abstract::The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have take...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5549
更新日期:1993-09-01 00:00:00
abstract::The inducer of short transcripts, or IST, is an unusual transcriptional element located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter. IST activates HIV-1 transcription, but the resulting RNAs are short and end at approximately position +59. IST, therefore, appears to promote the formation of ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.2.1251
更新日期:1993-02-01 00:00:00
abstract::Induction of differentiation in one type of clone of mouse myeloid leukemic cells by mouse or human interleukin 6 (IL-6) and in another type of clone by mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to be associated with induction of IL-6 and GM-CSF mRNA and protein. The results indicated t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.4109
更新日期:1989-09-01 00:00:00
abstract::Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size-reductive ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00053-16
更新日期:2016-07-14 00:00:00
abstract::Lactose or galactose induces the expression of the lactose-galactose regulon in Kluyveromyces lactis. We show here that the regulon is not induced in strains defective in LAC9. We demonstrate that this gene codes for a regulatory protein that acts in a positive manner to induce transcription. The LAC9 gene was isolate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1111
更新日期:1987-03-01 00:00:00
abstract::Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within chromatin. We report here the identification of a novel property of PARP as a modulator of nuclea...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2644
更新日期:1999-04-01 00:00:00
abstract::To identify novel genes that play critical roles in mediating bone morphogenetic protein (BMP) signal pathways, we performed a yeast two-hybrid screen using Smad1 as bait. A novel mouse Krüppel-type zinc finger protein, mZnf8, was isolated. Interactions between mZnf8 and Smad proteins were further analyzed with variou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.21.7633-7644.2002
更新日期:2002-11-01 00:00:00
abstract::TBC (Tre-2/Bub2/Cdc16) domains are predicted to encode GTPase-activating proteins (GAPs) for Rab family G proteins. While approximately 50 TBC proteins are predicted to exist in humans, little is known about their substrate specificity. Here we show that TRE17 (also called Tre-2 and USP6), a founding member of the TBC...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.22.9752-9762.2004
更新日期:2004-11-01 00:00:00
abstract::Erythroid Krüppel-like factor (EKLF [KLF1]) is a transcriptional regulator that plays a critical role within a specific subset of hematopoietic cells, particularly in the erythroid lineage and its immediate precursor, the megakaryocyte-erythroid progenitor (MEP). We find that EKLF is posttranslationally modified by su...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00589-07
更新日期:2007-12-01 00:00:00
abstract::Expression of the Cyp 2d-9 (steroid 16 alpha-hydroxylase) gene in mouse liver is male specific in such Mus musculus domesticus strains as FVB/N, whereas the corresponding P450 genes in the wild mouse species Mus spretus are not sex specific in their expression. These parental differences in the gene expressions were i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4158
更新日期:1995-08-01 00:00:00
abstract::There are four members of the myocyte enhancer factor 2 (MEF2) family of transcription factors in vertebrates, MEF2A, -B, -C, and -D, which have homology within a MADS box at their amino termini and an adjacent motif known as the MEF2 domain. These factors activate muscle gene expression by binding as homo- and hetero...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.2627
更新日期:1996-06-01 00:00:00
abstract::It is thought that degradation of nuclear proteins by the ubiquitylation system requires nuclear-cytoplasmic trafficking of E3 ubiquitin ligases. The von Hippel-Lindau (VHL) tumor suppressor protein is the substrate recognition component of a Cullin-2-containing E3 ubiquitin ligase that recruits hypoxia-inducible fact...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01044-07
更新日期:2008-01-01 00:00:00