PMID- 10330172
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 6
DP  - 1999 Jun
TI  - Evidence that tristetraprolin binds to AU-rich elements and promotes the
      deadenylation and destabilization of tumor necrosis factor alpha mRNA.
PG  - 4311-23
AB  - Mice deficient in tristetraprolin (TTP), the prototype of a family of CCCH zinc
      finger proteins, develop an inflammatory syndrome mediated by excess tumor
      necrosis factor alpha (TNF-alpha). Macrophages derived from these mice
      oversecrete TNF-alpha, by a mechanism that involves stabilization of TNF-alpha
      mRNA, and TTP can bind directly to the AU-rich element (ARE) in TNF-alpha mRNA
      (E. Carballo, W. S. Lai, and P. J. Blackshear, Science 281:1001-1005, 1998). We
      show here that TTP binding to the TNF-alpha ARE is dependent upon the integrity
      of both zinc fingers, since mutation of a single cysteine residue in either zinc 
      finger to arginine severely attenuated the binding of TTP to the TNF-alpha ARE.
      In intact cells, TTP at low expression levels promoted a decrease in size of the 
      TNF-alpha mRNA as well as a decrease in its amount; at higher expression levels, 
      the shift to a smaller TNF-alpha mRNA size persisted, while the accumulation of
      this smaller species increased. RNase H experiments indicated that the shift to a
      smaller size was due to TTP-promoted deadenylation of TNF-alpha mRNA. This CCCH
      protein is likely to be important in the deadenylation and degradation of
      TNF-alpha mRNA and perhaps other ARE-containing mRNAs, both in normal physiology 
      and in certain pathological conditions.
FAU - Lai, W S
AU  - Lai WS
AD  - Office of Clinical Research and Laboratory of Signal Transduction, National
      Institute of Environmental Health Sciences, Research Triangle Park, North
      Carolina 27709, USA.
FAU - Carballo, E
AU  - Carballo E
FAU - Strum, J R
AU  - Strum JR
FAU - Kennington, E A
AU  - Kennington EA
FAU - Phillips, R S
AU  - Phillips RS
FAU - Blackshear, P J
AU  - Blackshear PJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tristetraprolin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - EC 3.1.26.4 (Ribonuclease H)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Line
MH  - Cytosol/metabolism
MH  - *DNA-Binding Proteins
MH  - Dactinomycin/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Green Fluorescent Proteins
MH  - *Immediate-Early Proteins
MH  - Kinetics
MH  - Luminescent Proteins/metabolism
MH  - Macrophages/metabolism
MH  - Molecular Sequence Data
MH  - Plasmids
MH  - Precipitin Tests
MH  - Protein Processing, Post-Translational
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Proteins/metabolism/*pharmacology
MH  - RNA, Messenger
MH  - Recombinant Fusion Proteins
MH  - Ribonuclease H/metabolism
MH  - Tissue Distribution
MH  - Tristetraprolin
MH  - Tumor Necrosis Factor-alpha/*drug effects
MH  - Zinc Fingers
PMC - PMC104391
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1128/mcb.19.6.4311 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jun;19(6):4311-23. doi: 10.1128/mcb.19.6.4311.