Prothymosin alpha expression occurs during G1 in proliferating B or T lymphocytes

Department of Medicine, Cornell University Medical College, New York, NY 10021.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 07/1992; 185(3):953-9. DOI: 10.1016/0006-291X(92)91719-7
Source: PubMed


To gain insight into possible functions for prothymosin alpha in the proliferative cycle of lymphocytes, we examined the kinetics of prothymosin alpha mRNA expression in mitogen stimulated murine lymphocytes. This mRNA increases after mitogen stimulation, peaking in mid G1. This kinetics is compatible with induction of the prothymosin alpha gene by the c-myc protein (Eilers, M., Schirm, S. and Bishop, J.M. (1991) EMBO J., 10, 133-141). Thus, although prothymosin alpha mRNA is found throughout the cell cycle, the elevated expression in G1 may be associated with an increased requirement for prothymosin alpha during the G1/S transition or the S phase of the cell cycle.

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    • "Now prothymosin-h is suggested to have a role in cell proliferation. Prothymosin-h is present only in the cells that are in the proliferative cycle including the final steps of G1 phase, throughout the S and G2 phase, and in the initial steps of prophase, but is not expressed in non-proliferating cells [10]. Prothymosin-h gene expression was increased in human leukemic cells compared with normal peripheral blood lymphocytes [11]. "
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    ABSTRACT: Objective: Prothymosin-α, the precursor of thymosin-α1, may play a role in cell proliferation, and the plasma level of thymosin-α1 may reflect the degree of proliferation of the tumor cells. Methods: Recently, a new sandwich immunoradiometric assay for thymosin-α1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-α1 in 131 lung cancer patients. Results: We found that the mean plasma thymosin-α1 levels in lung cancer patients were higher than in normal individuals (P<0.001). However, half of the patients showed normal levels. Thymosin-α1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-α1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P=0.03). Survival of patients with normal levels of plasma thymosin-α1 was significantly better than that with higher levels (P=0.04). Conclusions: The plasma level of thymosin-α1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.
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    • "Stimulation of prothymosin a gene expression is associated with proliferation events. Prothymosin a mRNA is induced when cells proliferate in response to serum refeeding, mitogen stimulation or hormone stimulation (Eschenfeldt and Berger, 1986; Gomez-Marquez et al., 1989; Szabo et al., 1992; Alvarez et al., 1993), or as a consequence of c-myc activation (Eilers et al., 1991 ; Vareli et al., 1995). The finding that antisense oligonucleotides of prothymosin a mRNA inhibit cell division in myeloma RPMI 8226 cells is also indicative of the significant role this protein plays in proliferation (Sburlati et al., 1991). "
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    ABSTRACT: A number of studies have indicated that the small nuclear acidic protein prothymosin alpha is associated with cellular-proliferation events. For example, c-myc causes immediate transcriptional activation of prothymosin alpha, and prothymosin alpha antisense oligonucleotides inhibit myeloma cell division. To investigate the regulation of prothymosin alpha, we examined its mRNA and protein levels during the cell cycle of mononuclear cells and fibroblastic cells. We isolated immunoreactive material from cellular extracts and immunolocalized the protein to the nucleus during the cell cycle. We reported here that the material present in the cells is prothymosin alpha rather than the amino-terminal peptide thymosin alpha 1. [3H]Thymidine-incorporation studies associate maximum accumulation of mRNA and protein with the S/G2 phase of the cell cycle. This induction of prothymosin alpha mRNA seems to resemble cyclin B expression and is more pronounced in fibroblasts. Moreover, transient-transfection experiments indicate that transcription factor E2F is a strong positive regulator of the prothymosin alpha gene. Our results are consistent with the hypothesis that prothymosin alpha is involved in proliferation checkpoints of the cell cycle.
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