Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide.

Goldstein, Allan L.; Low, Teresa L. K.; McAdoo, Martha H.; McClure, John E.; Thurman, Gary B.; Rossio, Jeffrey L.; Lai, Chun‐Yen; Chang, David; Wang, Su-Sun; Harvey, Clifford; Ramel, A.; Meienhofer, Johannes

doi:10.1073/pnas.74.2.725

Cited by 315 publications

(131 citation statements)

References 26 publications

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“…The aforementioned group assumed that a protein remaining in the aqueous phase after extraction with phenol must be nucleic acid-bound; later, it was shown that prothymosin ␣ itself partitions to the aqueous phase and behaves chemically much like an RNA (Sburlati et al 1990). It is now fairly certain that a stable N-terminal acetyl group (Goldstein et al 1977;Michalewsky et al 1983;Haritos et al 1984;Sburlati et al 1993) and several highly labile glutamyl phosphate groups ), which are not retained in vitro, are the only physiological post-translational modifications. In addition, one study claiming that prothymosin ␣ stimulates the phosphorylation of translation factor eEF2 during mitosis (Vega et al 1998) has been rigorously challenged .…”

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confidence: 99%

Mobility Within the Nucleus and Neighboring Cytosol Is a Key Feature of Prothymosin-α

Enkemann

Ward

Berger

2000

J Histochem Cytochem.

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S U M M A R YProthymosin ␣ is a small, unfolded, negatively charged, poorly antigenic mammalian protein with a potent nuclear localization signal. Although it is apparently essential for growth, its precise function is unknown. We examined the location and behavior of the protein bearing different epitope tags using in situ immunolocalization in COS-1 and NIH3T3 cells. Tagged prothymosin ␣ appeared to be punctate and widely dispersed throughout the nucleus, with the exception of the nucleolus. A tiny cytoplasmic component, which persisted in the presence of cycloheximide and actinomycin D during interphase, became pronounced immediately before, during, and after mitosis. When nuclear uptake was abrogated, small tagged prothymosin ␣ molecules, but not prothymosin ␣ fused to ␤ -galactosidase, accumulated significantly in the cytoplasm. Tagged prothymosin ␣ shared domains with mobile proteins such as Ran, transportin, and karyopherin ␤ , which also traverse the nuclear membrane, and co-localized with active RNA polymerase II. Mild digitonin treatment resulted in nuclei devoid of prothymosin ␣ . The data do not support tight binding to any nuclear component. Therefore, we propose that prothymosin ␣ is a highly diffusible bolus of salt and infer that it facilitates movement of charged molecules in highly charged environments within and near the nucleus. T he function of prothymosin ␣ remains unclear despite many attempts to determine both its binding partners and its cellular location. Although the levels of the protein and its mRNA unquestionably increase in proliferating mammalian cells (Eschenfeldt and Berger 1986;Gómez-Márquez et al. 1989;Bustelo et al. 1991;Tsitsiloni et al. 1993), precisely what prothymosin ␣ does, where it does it, and what other macromolecules participate are questions with multiple unsatisfactory answers. The difficulties stem from three attributes: (a) Prothymosin ␣ is extremely acidic, with a net negative charge of ‫ف‬ 40 units (Eschenfeldt and Berger 1986;Goodall et al. 1986;Frangou-Lazaridis et al. 1988;Panneerselvam et al. 1988;Schmidt and Werner 1991). The large number of contiguous acidic amino acids in a protein of only ‫ف‬ 12 kD (Haritos et al. 1985), an unfolded conformation (Gast et al. 1995), and an abundance approaching that of histone cores (Palvimo and Linnala-Kankkunen 1990;Sburlati et al. 1990Sburlati et al. ,1993 make prothymosin ␣ an easy target for basic proteins in binding studies performed in vitro. The relevance of binding data is, accordingly, problematic. (b) Antibodies raised to prothymosin ␣ or peptides derived from it are invariably low in titer and broad in specificity. Such antibodies, particularly those directed against the N-terminus, crossreact with materials from crabs, insects, protozoans, fungi, and bacteria (Oates and Erdos 1989). However, the fully sequenced yeast genome does not code for prothymosin ␣ or related proteins, and homologous proteins in bacteria and homologous genes in a broad swath of the evolutionary spectrum up to and including reptiles h...

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confidence: 99%

Mobility Within the Nucleus and Neighboring Cytosol Is a Key Feature of Prothymosin-α

Enkemann

Ward

Berger

2000

J Histochem Cytochem.

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“…These include thymosin a,, an acidic peptide (pI = 4.2) containing 28 amino acid residues (6,7), and thymosin ,(4 (pI = 5.1) containing 44 amino acid residues (8). Each is modified by acetylation at the NH2 terminus.…”

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confidence: 99%

Thymosins beta 8 and beta 9: two new peptides isolated from calf thymus homologous to thymosin beta 4.

Hannappel¹,

Davoust²,

Horecker³

1982

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

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“…Bovine thymosin a 1 is an acidic peptide (M.W. 3108) with a pi of 4.2 (Goldstein et al, 1977). In humans, the concentration of thymosin a 1 in blood is highest in utero and decreases sharply after birth (McClure et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

In vivo effects of a thymosin α1-containing colostral whey product on neutrophils and lymphocytes from lactating cows without and with experimentally induced Staphylococcus aureus mastitis

Kehrli

Nonnecke

Wood

et al. 1989

Veterinary Immunology and Immunopathology

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Two separate experiments evaluated ID-1 (a commercial bovine whey product containing 5200 pg of thymosin α 1 /ml) as an immunotherapeutic agent in lactating cows. In the first experiment, cows without mastitis were evaluated for blood leukogram, milk production, total and differential milk cell counts, lymphocyte (Lc) blastogenesis, and neutrophil (PMN) functions (random and directed migration under agarose, chemiluminescence, ingestion of bacteria, iodination, cytochrome C reduction, antibodyindependent neutrophil-mediated cytotoxicity, and antibody-dependent cell-mediated cytotoxicity) before and after ID-1 therapy. ID-1 treatment resulted in a significant treatment group by time period interaction for the relative proportion of mononuclear cells (MNC) in milk (P<0.009) and for PMN random migration (P<0.01). Based on these interactions, ID-1 treatment appeared to slightly increase the proportion of small MNC in milk and to increase random migration from pretreatment levels by 73% more than increases observed in controls. No significant effect of ID-1 treatment on milk production, total milk somatic cell counts, Lc blastogenesis, or other PMN functions was observed. In cows with experimental Staphylococcus aureus intramammary infections, ID-1 treatment resulted in a significant decline in blood leukocyte count (P<0.001) and blood PMN count (P<0.02), and maintained PMN random migration (P<0.01) while controls declined and abrogated a depression in the ability of Lc to respond to mitogens (P<0.05) that developed in controls as a result of S. aureus mastitis. Injection of ID-1 into cows had no adverse effect on their overall health or level of milk production, but did cause subtle and potentially favorable changes in several in vitro immune parameters. In spite of these subtle changes which might indicate increased resistance to mastitis, cows actually developed a more severe S. aureus intramammary infection based on a 9% increase in log 10 bacterial shedding in milk. Veterinary Immunology and Immunopathology, 20 ( 1989) Two separate experiments evaluated ID-1 (a commercial bovine whey product containing 5200 pg ofthymosin a 1 /ml) as an immunotherapeutic agent in lactating cows. In the first experiment, cows without mastitis were evaluated for blood leukogram, milk production, total and differential milk cell counts, lymphocyte (Lc) blastogenesis, and neutrophil (PMN) functions (random and directed migration under agarose, chemiluminescence, ingestion of bacteria, iodination, cytochrome C reduction, antibody-independent neutrophil-mediated cytotoxicity, and antibody-dependent cell-mediated cytotoxicity) before and after ID-1 therapy. ID-1 treatment resulted in a significant treatment group by time period interaction for the relative proportion of mononuclear cells (MNC) in milk (P < 0.009) and for PMN random migration (P < 0.01). Based on these interactions, ID-1 treatment appeared to slightly increase the proportion of small MNC in milk and to increase random migration from pretreatment levels by 73% m...

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Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide.

Cited by 315 publications

References 26 publications

Mobility Within the Nucleus and Neighboring Cytosol Is a Key Feature of Prothymosin-α

Mobility Within the Nucleus and Neighboring Cytosol Is a Key Feature of Prothymosin-α

Thymosins beta 8 and beta 9: two new peptides isolated from calf thymus homologous to thymosin beta 4.

In vivo effects of a thymosin α1-containing colostral whey product on neutrophils and lymphocytes from lactating cows without and with experimentally induced Staphylococcus aureus mastitis

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