Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Elevated expression of
ornithine decarboxylase
(
ODC
) and increased synthesis of polyamines are hallmarks of epithelial tumorigenesis. The skin and tumors of K6/
ODC
and
ODC
/Ras transgenic mice, in which overexpression of
ODC
has been targeted to hair follicles, were found to exhibit intrinsically high histone acetyltransferase (HAT) activity. We identified
Tip60
as a candidate enzyme for contributing significantly to this abnormally high HAT activity. Compared with normal littermate controls, the levels of
Tip60
protein and an alternative splice variant Tip53 were found to be greater in K6/
ODC
mouse skin. Furthermore, skin tumors that spontaneously develop in
ODC
/Ras bigenic mice typically have substantially more
Tip60
protein than adjacent non-tumor-bearing skin and exhibit a unique pattern of
Tip60
size variants and chemically modified protein isoforms. Steady-state
Tip60
and Tip53 mRNA levels were not affected in
ODC
-overexpressing skin and tumors, implying novel posttranscriptional regulation by polyamines. Given the diverse roles of
Tip60
, the overabundance of
Tip60
protein is predicted to have biological consequences. Compared with normal littermate skin, we detected altered association of
Tip60
with E2F1 and a subset of newly identified
Tip60
-interacting transcription factors in
ODC
transgenic mouse skin and tumors. E2F1 was shown to be bound in greater amounts to up-regulated target genes in
ODC
-overexpressing skin. Thus, up-regulation of
Tip60
protein, influencing the expression of
Tip60
-regulated genes, could play a contributing role in polyamine-mediated tumor promotion. (
...
PMID:Tip60 protein isoforms and altered function in skin and tumors that overexpress ornithine decarboxylase. 1691 89
