Publication Date:
1998-08-14
Description:
Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of both acute and chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited TNF-alpha production from macrophages by destabilizing its messenger RNA. This effect appeared to result from direct TTP binding to the AU-rich element of the TNF-alpha messenger RNA. TTP is a cytosolic protein in these cells, and its biosynthesis was induced by the same agents that stimulate TNF-alpha production, including TNF-alpha itself. These findings identify TTP as a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carballo, E -- Lai, W S -- Blackshear, P J -- New York, N.Y. -- Science. 1998 Aug 14;281(5379):1001-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9703499" target="_blank"〉PubMed〈/a〉
Keywords:
3T3 Cells
;
Animals
;
Base Sequence
;
Biological Transport
;
Cell Line
;
Cell Nucleus/metabolism
;
Chick Embryo
;
Cytosol/metabolism
;
*DNA-Binding Proteins
;
Feedback
;
Gene Expression Regulation
;
Humans
;
*Immediate-Early Proteins
;
Lipopolysaccharides/pharmacology
;
Macrophages/*physiology
;
Mice
;
Mice, Knockout
;
Proteins/*physiology
;
RNA Probes
;
RNA, Messenger/chemistry/genetics/metabolism
;
Transfection
;
Tristetraprolin
;
Tumor Necrosis Factor-alpha/antagonists & inhibitors/*biosynthesis/genetics
;
*Zinc Fingers
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink