The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA.

Eschenfeldt, William H.; Berger, Shelby L.

doi:10.1073/pnas.83.24.9403

Cited by 184 publications

(145 citation statements)

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“…Together with our recent finding that overexpression of a-prothymosin is restricted to well-defined tumour nodules and to vaso-invading cancer cells in rat HCC rather than to non-tumour regeneration nodules (Wu et al, 1997b), these data suggest that the enhanced transcription of a-prothymosin is associated with HCC. As other evidence supports the view that a-prothymosin is involved in cellular proliferation (Eschenfeldt and Berger, 1986;Eilers et al, 1991;Sburlati et al, 1991), we considered the possibility that overexpression of a-prothymosin might be due to benign liver regeneration nodules that may coexist in HCC tissue. To test this possibility, we have studied mRNA levels of a-prothymosin in patients with only cirrhosis and in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…However, an accumulating body of evidence suggests that a-prothymosin is associated with cell proliferation, although the precise mechanism remains to be elucidated. For instance, a-prothymosin mRNA was found in proliferating lymphoma and transformed 3T3 fibroblast cells but not in resting cells (Eschenfeldt and Berger, 1986), and antisense RNA or synthetic antisense DNA oligomers of a-prothymosin were able to inhibit cell division in myeloma cells (Sburlati et al, 1991). More interestingly, a-prothymosin gene transcription was shown to be directly regulated by activated c-myc in vitro (Eilers et al, 1991) via an E-box element localized in the first intron of the a-prothymosin gene (Gaubatz et al, 1994).…”

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confidence: 99%

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Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma

Na²,

Mitry³

et al. 1997

Br J Cancer

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Summary Identification of gene products exclusively or abundantly expressed in cancer may yield novel tumour markers. We recently isolated a number of cDNA clones, including a-prothymosin, from rat hepatocellular carcinoma (HCC) using a subtraction-enhanced display technique. a-Prothymosin is involved in cell proliferation and is regulated by the oncogene c-myc in vitro. In the present study, we analysed a-prothymosin gene expression and its correlation with c-myc in patients with HCC, cirrhosis and adenoma and in normal controls. Hepatic aprothymosin messenger RNA (mRNA) levels were two-to 9.2-fold higher in tumoral tissues than in adjacent non-tumoral tissues in 14 of 17 patients with HCC, regardless of coexisting cirrhosis and viral hepatitis. No marked difference in a-prothymosin mRNA levels was present in patients with adenoma and hepatic cirrhosis and in healthy controls. The c-myc mRNA amounts were two-to fivefold increased in 11 of 17 patients with HCC and correlated significantly with those of a-prothymosin (P < 0.001). In situ hybridization revealed that increased aprothymosin mRNA was localized in the tumour nodules of the patients with HCC. These data suggest that overexpression of a-prothymosin in HCC patients, correlated with c-myc, is possibly involved in the tumorigenic process and may be a novel molecular marker for human HCC.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma

Na²,

Mitry³

et al. 1997

Br J Cancer

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“…More than 10,000 copies per cell of ProTα are found in kidney, liver, spleen, normal lymphocytes (predominantly T cells), human T-cell leukemia virus-infected T cells and myeloma cells (B-cell lineage) (Eschenfeldt and Berger, 1986). Several studies have demonstrated ProTα's function in immune regulatory activity and potentiation of the immune system (Cordero et al, 1991;Oates et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Characterization of two thymosins as immune-related genes in common carp (Cyprinus carpio L.)

Xiao

Shen

Hong

et al. 2015

Developmental & Comparative Immunology

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“…The protein is neither a precursor for processed polypeptides nor specifically associated with the thymus nor a member of a family with ␤ or ␥ homologues (1)(2)(3). Instead, it is probably the most acidic naturally occurring polypeptide in the eukaryotic world, with 54 carboxyl groups in 109 amino acids, resulting in an isoelectric point at or below pH 3.5 (1,2,4). The mRNA for prothymosin ␣ is distributed ubiquitously among mammalian nucleated cells and tissues (1).…”

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confidence: 99%

Prothymosin α in Vivo Contains Phosphorylated Glutamic Acid Residues

Trumbore

Wang

Enkemann

et al. 1997

Journal of Biological Chemistry

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2) Immediately upon cell lysis, the pH stability curves of metabolically labeled native [ 32 P]prothymosin ␣ or a [ 32 P]histidine-tagged variant resembled the pH stability curve of acetyl phosphate. 3) After a brief incubation at pH 7, these curves changed from a pattern diagnostic for an acyl phosphate to that characteristic of a serine or threonine phosphate, an observation consistent with transfer of phosphate in vitro. Our data indicate that most of prothymosin ␣'s phosphates are subject instantaneously to hydrolysis, based on the observation that greater than 90% of the phosphate initially found at pH 7 disappeared at the extremes of pH. Rapid loss of phosphate was not affected by the presence of phosphatase inhibitors including 50 mM sodium fluoride, 1 mM okadaic acid, and 0.5 mM calyculin A. The amount of phosphate missing could not be ascertained, but the trifling amount recovered on Ser or Thr depended heavily on conditions favoring the transient survival of labile phosphate. Further analysis using COS cells lysed in the presence of sodium borohydride showed that: 1) phosphate recovered on prothymosin ␣ decreased 8-fold when lysates were treated with borohydride; 2) the reagent caused 4 -8 glutamic acid residues/molecule to vanish; 3) using [ 3 H]NaBH 4 , label was introduced into proline, a product derived from reductive cleavage of phosphoglutamate; and 4) [ 3 H]proline was localized almost exclusively to a peptide with pronounced homology to the histone binding site of nucleoplasmin, a chromatin remodeling protein found in Xenopus laevis. Our data demonstrate that prothymosin ␣ is energy-rich by virtue of stoichiometric amounts of glutamyl phosphate.Prothymosin ␣ is a highly unusual protein with an unfortunate name. The protein is neither a precursor for processed polypeptides nor specifically associated with the thymus nor a member of a family with ␤ or ␥ homologues (1-3). Instead, it is probably the most acidic naturally occurring polypeptide in the eukaryotic world, with 54 carboxyl groups in 109 amino acids, resulting in an isoelectric point at or below pH 3.5 (1, 2, 4). The mRNA for prothymosin ␣ is distributed ubiquitously among mammalian nucleated cells and tissues (1). The protein possesses a potent nuclear localization signal and is present in amounts equivalent to those of histone H1 (5, 6). Because the amount of prothymosin ␣ mRNA (and presumably protein) found in a cell is directly proportional to cell growth, the protein is believed to play a role in cell proliferation (1). This idea was reinforced by the observation that synchronized human myeloma cells, in the presence of antisense oligodeoxyribonucleotides directed at prothymosin ␣ mRNA, were unable to divide while detectable amounts of the antisense oligonucleotides remained inside the cell (7). There are now many examples of a link between prothymosin ␣ and growth in systems as diverse as developing mouse embryos (8); normal, mitogenstimulated, and malignant lymphocytes (9, 10); and regenerating liver (10). There are also positive ...

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The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA.

Cited by 184 publications

References 35 publications

Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma

Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma

Characterization of two thymosins as immune-related genes in common carp (Cyprinus carpio L.)

Prothymosin α in Vivo Contains Phosphorylated Glutamic Acid Residues

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