Linked Life Data

11691585

Source:http://linkedlifedata.com/resource/pubmed/id/11691585

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-11-5
pubmed:abstractText
The transcription factor cKrox was originally identified as a protein that bound to a negative transcription regulatory element in the murine alpha1(I) collagen promoter. We recently reported the cloning and characterization of human cKrox (hcKrox). Overexpression of hcKrox in NIH3T3 fibroblasts efficiently repressed the promoters of the fibronectin and alpha1(I) collagen genes (70-90%) in transient transfection assays and suppressed the endogenous genes in hcKrox expressing permanent cell lines. We have now isolated genomic clones and cDNAs encoding two novel transcription factors related to hcKrox termed hcKrox-beta and hcKrox-gamma (the original clone is now referred to as hcKrox-alpha). Both contain three kruppel-like zinc-finger DNA binding motifs that are 71-78% identical to those of hcKrox-alpha. The NH(2)-terminus of all three proteins contains a POZ domain, a conserved 120 amino acid motif involved in transcriptional repression and protein dimerization. RT-PCR experiments demonstrate that all three hcKrox family members are expressed in foreskin and dermal fibroblasts. Transient transfection studies in NIH3T3 fibroblasts demonstrate that hcKrox-alpha -beta and -gamma, as well as the murine cKrox-beta homologue, LRF, suppress transcription driven by promoters for the alpha1(I) and alpha2(I) collagen, fibronectin and elastin genes. Electrophoretic mobility shift assays and coimmunoprecipitation studies suggest that homo- and heterodimerization occurs between cKrox family members. Dimer formation is influenced by amino acids in the NH(2)-terminal POZ domain and the Zn(+2)-finger region. Immunoprecipitation studies indicate that cKrox can form heterodimers in solution in the absence of DNA. Thus, a multi-gene family exists that can coordinately regulate several extracellular matrix genes and has the potential to form many heterodimeric transcription factors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0945-053X
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
451-62
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11691585-3T3 Cells, pubmed-meshheading:11691585-Amino Acid Sequence, pubmed-meshheading:11691585-Animals, pubmed-meshheading:11691585-COS Cells, pubmed-meshheading:11691585-Cercopithecus aethiops, pubmed-meshheading:11691585-Collagen Type I, pubmed-meshheading:11691585-DNA, pubmed-meshheading:11691585-DNA-Binding Proteins, pubmed-meshheading:11691585-Dimerization, pubmed-meshheading:11691585-Elastin, pubmed-meshheading:11691585-Fibronectins, pubmed-meshheading:11691585-Gene Expression Regulation, pubmed-meshheading:11691585-Humans, pubmed-meshheading:11691585-Mice, pubmed-meshheading:11691585-Molecular Sequence Data, pubmed-meshheading:11691585-Multigene Family, pubmed-meshheading:11691585-Promoter Regions, Genetic, pubmed-meshheading:11691585-Repressor Proteins, pubmed-meshheading:11691585-Sequence Homology, Amino Acid, pubmed-meshheading:11691585-Transcription Factors, pubmed-meshheading:11691585-Zinc Fingers
pubmed:year
2001
pubmed:articleTitle
The hcKrox gene family regulates multiple extracellular matrix genes.
pubmed:affiliation
Arthritis Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. rwidom@medicine.bu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't