Prothymosin α is an evolutionary conserved protein covalently linked to a small RNA

Makarova, Tatyana N.; Grebenshikov, Nickolay; Egorov, Cesiy; Vartapetian, Andrey B.; Bøgdanov, A.

doi:10.1016/0014-5793(89)81544-3

Cited by 54 publications

(58 citation statements)

References 11 publications

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“…Further studies demonstrated that PTMA is present in a large variety of cell types, tissues, and organisms (Haritos et al, 1984b;Eschenfeldt and Berger, 1986;Clinton et al, 1989;Gomez-Marquez et al, 1989). The high degree of conservation of PTMA among species (Makarova et al, 1989) further suggests that it may be required for essential cell functions. Although its precise biological role has not been assigned yet, a number of in vivo (Dominguez et al, 1993) and in vitro studies (Gomez-Marquez et al, 1989;Bustelo et al, 1991;Sburlati et al, 1991) correlated PTMA with proliferative activities.…”

Section: Discussionmentioning

confidence: 99%

Identification of Estrogen-Responsive Genes in Neuroblastoma SK-ER3 Cells

et al. 1997

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To evaluate the role of estrogen receptor in the differentiation of cells of neural origin, we developed a molecular approach aimed at the identification of estrogen target genes by mRNA differential display PCR (ddPCR) in human neuroblastoma SK-ER3 cells. More than 3000 RNAs were examined, a few of which displayed a differential regulation pattern in response to 17␤-estradiol (E 2 ). Sequence analysis of three differentially amplified ddPCR products showed homology with the growthassociated nuclear protein prothymosin-␣ (PTMA), the Bcl2-interacting protein Nip2, and one mRNA previously described by others in fetal human brain. Two ddPCR products, referred to as P4 and P10, corresponded to new DNA sequences. Northern analysis confirmed that estrogen treatment of SK-ER3 cells resulted in the upregulation and downregulation of expression of these messages. In particular, PTMA was found to accumulate at both 1 and 17 hr after E 2 treatment, whereas P10 product accumulated only at 1 hr. Conversely, P4, Nip2, and the fetal brain-related mRNAs were significantly decreased by the treatment. Further time course analysis of PTMA and Nip2 mRNAs levels indicated that the hormone exerted a marked biphasic regulatory effect on expression of both messages during the course of cell differentiation. In the present study we report for the first time the identification of a panel of estrogen target genes in neural cells that provide new insights in the molecular mechanism of action of E 2 in cells of neural origin.

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Section: Discussionmentioning

confidence: 99%

Identification of Estrogen-Responsive Genes in Neuroblastoma SK-ER3 Cells

et al. 1997

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“…Interestingly, using a microinjection technique, Watts et al showed recently that ProTa purified from whole calf thymus cells migrates into Xenopus oocyte nucleus at a rate comparable to that of histone Hl [22]. ProTcv remained stable in the nucleus for 48 h. ProTa has also been identified from cytoplasm of mouse cells as a protein covalently linked to a small RNA [23]. No information on the subcellular localization of the RNA/protein linking reaction is available.…”

Section: Discussionmentioning

confidence: 99%

Identification of a low‐M_r acidic nuclear protein as prothymosin α

Palvimo¹,

Linnala-Kankkunen²

1990

FEBS Letters

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We have purified to homogeneity a lij-kDa perchloric acid (PCA)-soluble protein from rat thymus nuclei. This highly acidic protein showed a M, of ca. 30 kDa in acetic acid/urea gels, probabty due to oligomer formation. Sequence analysis of internal tryptic and the~ol~c peptides revealed that the purified protein is, in fact, prothymosin u, a very hydrophilic polypeptide, which has been previously classified as a thymic or immunomodulating hormone. We found that prothymosin G( is a rather abundant nuclear protein in rat thymus; its concentration is comparable to that of a well-characterized nonhistone protein HMG-14. The subcellular localization and physicochemical properties of prothymosin c( suggest that its function is related to those of other long polyacidic regions containing nuclear proteins.

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“…Evidence from this and other laboratories suggests that the protein is neither a precursor of thymosin a,, a putative thymic hormone, nor a secreted thymic hormone itself (1)(2)(3). Instead, several observations support a role in cell proliferation: (i) Prothymosin a mRNA and protein are present in virtually all mammalian tissues, and a homologous protein has been detected in yeast (1,(4)(5)(6)(7)(8); these findings are consistent with an activity essential to most cells. (ii) The amounts of prothymosin a and its mRNA are roughly proportional to the proliferative activity of the tissue from which they are isolated (1,4,7).…”

Section: Introductionmentioning

confidence: 98%

Prothymosin alpha antisense oligomers inhibit myeloma cell division.

Sburlati

Manrow²,

Berger³

1991

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

147

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The function of prothymosin a has been investigated by using four different antisense oligodeoxyribonucleotides directed at selected regions of its mRNA. In every case, when synchronized human myeloma cells were released from stationary phase by incubation in fresh medium containing antisense oligomers, cell division was prevented or inhibited; sense oligomers and random antisense oligomers had no effect. A detailed analysis of synchronized cell populations indicated that sense-treated and untreated cells divided m17 hr after growth initiation, whereas cells incubated with antisense oligomer 183, a 16-mer targeted 5 bases downstream of the initiation codon, entered mitosis approximately one cell division late. The failure to divide correlated directly with a deficit in prothymosin a and with the continued presence of intact intracellular antisense oligomers over a period ofat least 24 hr. Because antisense oligomers had no effect either on the timing of the induction of prothymosin a mRNA upon growth stimulation or on mRNA levels seen throughout the cell cycle, we concluded that antisense DNA caused specific hybrid arrest of translation. Our data suggest that prothymosin a is required for cell division. However, there is no evidence that prothymosin a directly regulates mitosis.The function of prothymosin a is debatable. Evidence from this and other laboratories suggests that the protein is neither a precursor of thymosin a,, a putative thymic hormone, nor a secreted thymic hormone itself (1-3). Instead, several observations support a role in cell proliferation: (i) Prothymosin a mRNA and protein are present in virtually all mammalian tissues, and a homologous protein has been detected in yeast (1,(4)(5)(6)(7)(8); these findings are consistent with an activity essential to most cells. (ii) The amounts of prothymosin a and its mRNA are roughly proportional to the proliferative activity of the tissue from which they are isolated (1,4,7). (iii) Prothymosin a mRNA is induced in normal human lymphocytes and in serum-starved NIH 3T3 cells upon growth stimulation with mitogens or serum, respectively (1).Using COS cells transfected with the human prothymosin a gene, we have recently shown that prothymosin a is a nuclear protein. We have also found that chimeric proteins composed of all or part of prothymosin a fused with (3-galactosidase are targeted to the nucleus only when the basic amino acids at the carboxyl terminus of prothymosin a are included (9). The presence of a nuclear localization signal indicates a function carried out, at least in part, in the nucleus; the precise nature of that function is unknown.In the present study, we have directly evaluated the relationship between prothymosin a and cell division. Using antisense oligomers to inhibit accumulation ofprothymosin a in a synchronized population of myeloma cells, we have established that cells deficient in prothymosin a cannot divide, that the inhibition is reversible, and that degradation of intracellular antisense oligomers accompanies resumpti...

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Prothymosin α is an evolutionary conserved protein covalently linked to a small RNA

Cited by 54 publications

References 11 publications

Identification of Estrogen-Responsive Genes in Neuroblastoma SK-ER3 Cells

Identification of Estrogen-Responsive Genes in Neuroblastoma SK-ER3 Cells

Identification of a low‐M_r acidic nuclear protein as prothymosin α

Prothymosin alpha antisense oligomers inhibit myeloma cell division.

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Prothymosin α is an evolutionary conserved protein covalently linked to a small RNA

Cited by 54 publications

References 11 publications

Identification of Estrogen-Responsive Genes in Neuroblastoma SK-ER3 Cells

Identification of Estrogen-Responsive Genes in Neuroblastoma SK-ER3 Cells

Identification of a low‐Mr acidic nuclear protein as prothymosin α

Prothymosin alpha antisense oligomers inhibit myeloma cell division.

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Identification of a low‐M_r acidic nuclear protein as prothymosin α