RESUMO
Programmed cell death occurs in every multicellular organism and in diverse cell types yet the genetic controls that define which cells will live and which will die remain poorly understood. During development of the nematode Caenorhabditis elegans, the coordinated activity of four gene products, EGL-1, CED-9, CED-4 and CED-3, results in the death of essentially all cells fated to die. To identify novel upstream components of the cell death pathway, we performed a genetic screen for mutations that abolish the death of the hermaphrodite-specific neurons (HSNs), a homologous pair of cells required for egg-laying in the hermaphrodite. We identified and cloned the genes, eor-1 and eor-2, which are required to specify the fate of cell death in male HSNs. In addition to defects in HSN death, mutation of either gene leads to defects in coordinated movement, neuronal migration, male tail development, and viability; all consistent with abnormal neuronal differentiation. eor-1 encodes a putative transcription factor related to the human oncogene PLZF. eor-2 encodes a novel but conserved protein. We propose that eor-1 and eor-2 function together throughout the nervous system to promote terminal differentiation of neurons and function specifically in male HSNs to promote apoptotic death of the HSNs.
Assuntos
Apoptose/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Proteínas Nucleares/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Diferenciação Celular/fisiologia , Primers do DNA , Feminino , Proteínas de Fluorescência Verde , Proteínas Luminescentes/metabolismo , Dados de Sequência Molecular , Mutação/genética , Neurônios/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Reação em Cadeia da Polimerase , Proteínas Repressoras/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Two serine carboxypeptidases (EC 3.4.16.5) were purified from mung bean seedling cotyledons. Sequences of tryptic peptides derived from the 42.5 kD enzyme corresponded to the derived amino acid sequence of a sequenced cDNA (GenBank U49382 and U49741). This enzyme exhibited the substrate specificity pattern previously published for mung bean carboxypeptidase I. In comparison, the sequence and substrate specificity data obtained for the 43 kD enzyme were similar but not identical. Both enzymes showed preference for peptide substrates with a large hydrophobic residue at the C-terminus. With regard to the penultimate residue of peptide substrates, the mung bean carboxypeptidase I preferred small aliphatic amino acid residues, while the 43 kD enzyme preferred large hydrophobic ones.
