Disease relevance of Zfp36

• We report here the nucleotide sequence of a rat TIS11 cDNA, an immediate early gene, induced by nerve growth factor and epidermal growth factor, by 12-O-tetradecanoyl phorbol-13-acetate, and other stimuli in PC12 pheochromocytoma cells [1].
• When fused to the luciferase reporter gene, the 5.3-kb 5'-flanking region of the rat TIS11 gene exhibited functional promoter activity in pheochromocytoma PC12 and hepatoma H4IIE cells [2].
• The experiment continued for over 500 days, and was evaluated by comparing, between groups, the time taken for the development of objective signs of colonic disease (time to tumour presentation or TTP) [3].
• Thus, the toxicity of AZT in some tissues may be mediated by disrupting the substrate supply of TTP for mt-DNA replication [4].

High impact information on Zfp36

• In contrast, these receptors retained the ability to mediate NGF-promoted survival and TIS8 and TIS11 immediate-early gene induction [5].
• The effects of the purines, adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate (GTP), and the pyrimidines, uridine 5'-triphosphate (UTP), cytidine 5'-triphosphate (CTP), and thymidine 5'-triphosphate (TTP), on vascular resistance were investigated in the rat mesenteric arterial bed [6].
• In raised-tone preparations, vasodilator responses to ATP, UTP, TTP, and GTP were abolished after removal of the endothelium with sodium deoxycholate [6].
• When tone was raised with norepinephrine (30 microM), these agents caused dose-related vasodilatation with the potency order of UTP = ATP greater than TTP = GTP [6].
• In preparations at basal tone, these agents produced dose-related vasoconstriction with a potency order of ATP greater than CTP greater than UTP much greater than TTP = GTP [6].

Biological context of Zfp36

• Recruitment of mRNA-destabilizing protein TIS11 to stress granules is mediated by its zinc finger domain [7].
• By deletion studies using the green fluorescent protein fusion system, we mapped a functional stress granule (SG) localization signal to a region containing two tandem repeats of the zinc finger motif of TIS11 [7].
• Sequence of a rat TIS11 cDNA, an immediate early gene induced by growth factors and phorbol esters [1].
• Identification of nuclear import and export signals within the structure of the zinc finger protein TIS11 [8].
• The rat TIS11 gene consisted of 2 exons spanning approximately 2.5 kb [9].

Anatomical context of Zfp36

• TIS11, a member of the CCCH zinc finger protein family, was found to be distributed throughout cells with a preferential cytoplasmic localization when transiently expressed in COS-7 cells [7].
• We showed the TIS11-positive particles to be stress granules (SGs), which are known to be formed in the cytoplasm of eukaryotic cells in response to environmental stresses [7].
• The identified nuclear protein components may act as the positive trans-acting factors in the basal expression of the TIS11 gene in PC12 cells [9].
• Database searches have revealed no similarities between cMG1 and other genes, except that over a 67-amino acid region the cMG1 protein shows 72% identity to the product of the TIS11 gene, a TPA-induced sequence in Swiss 3T3 cells [10].
• The potency of nucleotides to raise [Ca2+]i was ATP gamma S > or = UDP > or = ATP approximately UDP approximately TTP, indicating that P2u receptors were expressed in the rat basilar smooth muscle cells [11].

Associations of Zfp36 with chemical compounds

• Site-directed mutations of Tyr105/Tyr113, Gly109/Gly 114, and Phe119 in the first zinc finger motif diminished the ability of this TIS11 domain to direct SG localization [7].
• Importantly, when the zinc-chelating Cys residues in either the first or second zinc finger were mutated to Ala residues, the recruitment of the TIS11 zinc finger region to SG was significantly inhibited by the mutation and was completely abolished by the mutation in both zinc fingers [7].
• A site-directed mutagenesis analysis of TIS11 NLS has revealed the critical importance of two arginine residues (Arg127 and Arg131 in the rat TIS11) [8].
• Upon treatment with leptomycin B, a specific inhibitor of the nuclear export receptor CRM1, a marked nuclear accumulation of TIS11 was observed, indicating that TIS11 shuttles between the nucleus and the cytoplasm [8].
• The selective P2 X-purinoceptor-desensitizing agent alpha,beta-methylene ATP inhibited vasoconstrictor responses to ATP and to CTP but had no effect on vasoconstrictor responses elicited by UTP, TTP, and GTP [6].

Other interactions of Zfp36

• The time course of the induction of NGFI-A, NGFI-B, fra-2 and TIS11 was similar to that previously observed with c-fos and the members of the jun family [12].
• Galanin was found to induce c-fos, junB, and Tis11 mRNA in cultured astrocytes, providing evidence for the presence of functional galanin receptors on neuroglial cells [13].
• RNAs from several brain regions were analyzed by Northern blot hybridization for their relative concentrations of nine IEG mRNAs (c-fos, c-jun, junB, TIS 1 (nur77), TIS7, TIS8 (zif268), TIS10, TIS11, and TIS21) [14].

Analytical, diagnostic and therapeutic context of Zfp36

• Gel mobility shift assays revealed that PC12 cell nuclear proteins specifically bind to the major positive regulatory region of the TIS11 gene [9].
• The three axotomy-induced messenger RNAs, c-jun, jun B and TIS 11, were all localized in the facial motoneurons by in situ hybridization histochemistry indicating that their induction occurs as part of the retrograde reaction of the motoneurons in response to lesion [15].
• A rapid and transient increase in c-fos, junB, c-jun and Tis11 messenger RNA was observed in cultured astrocytes after treatment with adenosine-5'-O-(2-thiodiphosphate) [16].

References