Proapoptotic role of novel gene-expression factors.

The mechanisms that control cellular proliferation, as well as those related with programmed cell death or apoptosis, require precise regulation systems to prevent diseases such as cancer. Events related to cellular proliferation as well as those associated with apoptosis involve the regulation of gene expression carried out by three basic genetic expression regulation mechanisms: transcription, splicing of the primary transcript for mature mRNA formation, and RNA translation, a ribosomal machinery-dependent process for protein synthesis. While development of each one of these processes requires energy for recognition and assembly of a number of molecular complexes, it has been reported that an increased expression of several members of these protein complexes promotes apoptosis in distinct cell types. The question of how these factors interact with other proteins in order to incorporate themselves into the different transduction cascades and stimulate the development of programmed cell death, although nowadays actively studied, is still waiting for a clear-cut answer. This review focuses on the interactions established between different families of transcription, elongation, translation and splicing factors associated to the progression of apoptosis.

Proapoptotic role of novel gene-expression factors

The mechanisms that control cellular proliferation, as well as those related with programmed cell death or apoptosis, require precise regulation systems to prevent diseases such as cancer. Events related to cellular proliferation as well as those associated with apoptosis involve the regulation of gene expression carried out by three basic genetic expression regulation mechanisms: transcription, splicing of the primary transcript for mature mRNA formation, and RNA translation, a ribosomal machinery-dependent process for protein synthesis. While development of each one of these processes requires energy for recognition and assembly of a number of molecular complexes, it has been reported that an increased expression of several members of these protein complexes promotes apoptosis in distinct cell types. The question of how these factors interact with other proteins in order to incorporate themselves into the different transduction cascades and stimulate the development of programmed cell death, although nowadays actively studied, is still waiting for a clear-cut answer. This review focuses on the interactions established between different families of transcription, elongation, translation and splicing factors associated to the progression of apoptosis (AU)

ARP2 a novel protein involved in apoptosis of LNCaP cells shares a high degree homology with splicing factor Prp8.

The mechanism of apoptosis has been recognized as an important event in processes such as cellular development and homeostasis, as well as degenerative conditions like cancer. Prostate cancer during its advanced stages develops androgen independent cells that ultimately overgrow and promote metastatic events. Our group employing androgen independent LNCaP cells have previously proposed, based on electrophysiological findings, that apoptosis induced cells overexpress a cell death calcium channel-like molecule. Here we report the cloning and expression in Xenopus laevis oocytes of apoptosis regulated protein 2 (ARP2), a protein overexpressed in apoptosis induced LNCaP cells capable to induce calcium inward currents and apoptosis typical morphology changes in oocytes injected with arp2 mRNA. Our results also indicate that clone arp2 cDNA (1.3Kb) shares a 99% homology with a small fragment that corresponds to 18% of the complete sequence of Prp8 cDNA (7.0 Kb), a molecule that codifies for an important protein in the assembly of the spliceosome. We propose that protein ARP2 as a fragment of protein Prp8, corresponds to a molecule with a new function in apoptosis related phenomena.

Apoptosis and cell death channels in prostate cancer.

Apoptosis, a type of programmed cell death, is a decisive mechanism in cell processes such as homeostasis, development, and many diseases including cancer. In mammals, the mechanisms that trigger and control the process of apoptosis are complex, because it has been observed that many molecules might be involved, acting in distinct ways and depending on the cellular type. The process of apoptosis is characterized by specific biochemical and morphologic changes. However, important specific messengers such as Ca(2)+ act in active proliferation as well as in apoptosis. At present, there is convincing evidence that a sustained increase in intracellular Ca(2)+ can activate cytotoxic mechanisms in various cells and tissues. Several ionic channels located in the cytoplasmic membrane might participate in the entry of calcium into the cytosol during apoptosis. Among these ionic channels, the purinoreceptors P2X and the channels of capacitative entry of calcium have been described. Pro- and anti-apoptotic molecules such as bax and bcl-2, respectively, have also been shown to participate in the process. We have recently found the activation of a Ca(2)+-permeable, nonselective cation channel of 23 pS conductance in prostatic cancer (LNCaP) exclusively in cells previously induced to apoptosis. Our findings are discussed taking into account the different ion channels that might participate in programmed cell death in prostate cancer.