Thymosins: both nuclear and cytoplasmic proteins

Watts, Julian D.; Cary, Peter D.; Sáutière, Pierre; Crane‐Robinson, Colyn

doi:10.1111/j.1432-1033.1990.tb19271.x

Cited by 85 publications

(94 citation statements)

References 48 publications

(5 reference statements)

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“…NMR spectroscopy. The spectra of p8 and ProT␣ showed typical features of random-coil chains (5,24,25): All of the amide protons appeared clustered between 8.0 and 8.7 ppm (Fig. 1D), with complete lack of dispersion in the methyl region (Fig.…”

Section: Resultsmentioning

confidence: 99%

Regulation of apoptosis by the p8/prothymosin α complex

Malicet

Giroux

Vasseur

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

113

100

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p8 is a small-stress protein involved in several cellular functions including apoptosis. To identify its putative partners, we screened a HeLa cDNA library by using the two-hybrid technique and found that p8 binds the antiapoptotic protein prothymosin ␣ (ProT␣). Fluorescence spectroscopy, circular dichroism, and NMR spectroscopy showed that p8 and ProT␣ formed a complex. Binding resulted in important changes in the secondary and tertiary structures of the proteins. Because p8 and ProT␣ form a complex, they could act in concert to regulate the apoptotic cascade. We induced apoptosis in HeLa cells by staurosporine treatment and monitored the effects of knocking down p8 and͞or ProT␣ or overexpressing p8 and͞or ProT␣ on caspase 3͞7 and 9 activities and on cell death. Transfecting ProT␣ or p8 small interfering RNAs increased the activities of both caspases and the number of apoptotic nuclei. However, transfecting both small interfering RNAs resulted in no further increase. Overexpressing p8 or ProT␣ did not alter caspase activities, whereas overexpressing both resulted in a significant reduction of caspase activities. These results strongly suggest that the antiapoptotic response of HeLa cells upon staurosporine treatment requires expression of both p8 and ProT␣.caspases ͉ unfolded proteins ͉ CytoTrap ͉ stress proteins

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Section: Resultsmentioning

confidence: 99%

Regulation of apoptosis by the p8/prothymosin α complex

Malicet

Giroux

Vasseur

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

113

100

View full text Add to dashboard Cite

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“…The peculiar amino-acid composition of ProTa results in its exceptional acidity (pI < 3.5) and hydrophilicity, manifested by the unique ability of the protein to partition into the aqueous phase on phenol extraction [5,6]. Attempts to identify the elements of regular structure in ProTa using various approaches were unsuccessful and led to the conclusion that ProTa possesses a rare random coil conformation [7,8], at least under physiological conditions. ProTa was found in virtually all mammalian tissues studied, with the highest content in the thymus [9].…”

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confidence: 99%

Divalent metal cation binding properties of human prothymosin α

Chichkova

Evstafieva

Lyakhov

et al. 2000

European Journal of Biochemistry

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The divalent cation binding properties of human prothymosin a, an abundant nuclear protein involved in cell proliferation, were evaluated. By using prothymosin a retardation on a weak cation chelating resin charged with various divalent cations, specific binding of Zn 21 ions by prothymosin a was observed. This finding was further confirmed by the equilibrium dialysis analysis which demonstrated that, within the micromolar range of Zn 21 concentrations, prothymosin a could bind up to three zinc ions in the presence of 100 mm NaCl and up to 13 zinc ions in the absence of NaCl. Equilibrium dialysis analysis also revealed that prothymosin a could bind Ca 21 , although the parameters of Ca 21 binding by prothymosin a were less pronounced than those of Zn 21 binding in terms of the number of metal ions bound, the K D values, and the resistance of the bound metal ions to 100 mm NaCl. The effects of Zn 21 and Ca 21 on the interaction of prothymosin a with its putative partners, Rev of HIV type 1 and histone H1, were examined. We demonstrated that Rev binds prothymosin a, and that prothymosin a binding to Rev but not to histone H1 was significantly enhanced in the presence of zinc and calcium ions. Our data suggest that the modes of prothymosin a interaction with Rev and histone H1 are distinct and that the observed zinc and calcium-binding properties of prothymosin a might be functionally relevant.

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“…It is devoid of tyrosine, tryptophan, phenylalanine, histidine, methionine, and cysteine, with leucine, isoleucine, and proline residues occurring at only one location. There are seven widely dispersed hydrophobic residues, an architecture which makes a folded structure unlikely (58,59). An acidic subset with a marked resemblance to the presumed histone binding site of nucleoplasmin has been identified (15,21).…”

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confidence: 99%

Do Products of the myc Proto-Oncogene Play a Role in Transcriptional Regulation of the Prothymosin α Gene?

Mol

Wang

Batey

et al. 1995

Molecular and Cellular Biology

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The Myc protein has been reported to activate transcription of the rat prothymosin ␣ gene by binding to an enhancer element or E box (CACGTG) located in the first intron (S. Gaubatz et al., Mol. Cell. Biol. 14:3853-3862, 1994). The human prothymosin ␣ gene contains two such motifs: in the promoter region at kb ؊1.2 and in intron 1, ϳ2 kb downstream of the transcriptional start site in a region which otherwise bears little homology to the rat gene. Using chloramphenicol acetyltransferase (CAT) reporter constructs driven either by the 5-kb human prothymosin ␣ promoter or by a series of truncated promoters, we showed that removal of the E-box sequence had no effect on transient expression of CAT activity in mouse L cells. When intron 1 of the prothymosin ␣ gene was inserted into the most extensive promoter construct downstream of the CAT coding region, a diminution in transcription, which remained virtually unchanged upon disruption of the E boxes, was observed. CAT constructs driven by the native prothymosin ␣ promoter or the native promoter and intron were indifferent to Myc; equivalent CAT activity was observed in the presence of ectopic normal or mutant Myc genes. Similarly, expression of a transiently transfected wild-type prothymosin ␣ gene as the reporter was not affected by a repertoire of myc-derived genes, including myc itself and dominant or recessive negative myc mutants. In COS-1 cells, equivalent amounts of the protein were produced from transfected prothymosin ␣ genes regardless of whether genomic E boxes were disrupted, intron 1 was removed, or a repertoire of myc-derived genes was included in the transfection cocktail. More importantly, cotransfection of a dominant negative Max gene failed to reduce transcription of the endogenous prothymosin ␣ gene in COS cells or the wild-type transfected gene in COS or L cells. Taken together, the data do not support the idea that Myc activates transcription of the intact human prothymosin ␣ gene or reporter constructs that mimic its structure. Rather, they suggest that the human prothymosin ␣ promoter and downstream elements are buffered so as to respond poorly, if at all, to transient fluctuations in transcription factors which regulate other genes.

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Thymosins: both nuclear and cytoplasmic proteins

Cited by 85 publications

References 48 publications

Regulation of apoptosis by the p8/prothymosin α complex

Regulation of apoptosis by the p8/prothymosin α complex

Divalent metal cation binding properties of human prothymosin α

Do Products of the myc Proto-Oncogene Play a Role in Transcriptional Regulation of the Prothymosin α Gene?

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