The role of multifunctional M1 metallopeptidases in cell cycle progression

Abstract

† Background Metallopeptidases of the M1 family are found in all phyla (except viruses) and are important in the cell cycle and normal growth and development. M1s often have spatiotemporal expression patterns which allow for strict regulation of activity. Mutations in the genes encoding M1s result in disease and are often lethal. This family of zinc metallopeptidases all share the catalytic region containing a signature amino acid exopeptidase (GXMXN) and a zinc binding (HEXXH[18X]E) motif. In addition, M1 aminopeptidases often also contain additional membrane association and/or protein interaction motifs. These protein interaction domains may function independently of M1 enzymatic activity and can contribute to multifunctionality of the proteins. † Scope A brief review of M1 metalloproteases in plants and animals and their roles in the cell cycle is presented. In animals, human puromycin-sensitive aminopeptidase (PSA) acts during mitosis and perhaps meiosis, while the insect homologue puromycin-sensitive aminopeptidase (PAM-1) is required for meiotic and mitotic exit; the remaining human M1 family members appear to play a direct or indirect role in mitosis/cell proliferation. In plants, meiotic prophase aminopeptidase 1 (MPA1) is essential for the first steps in meiosis, and aminopeptidase M1 (APM1) appears to be important in mitosis and cell division. † Conclusions M1 metalloprotease activity in the cell cycle is conserved across phyla. The activities of the multifunctional M1s, processing small peptides and peptide hormones and contributing to protein trafficking and signal transduction processes, either directly or indirectly impact on the cell cycle. Identification of peptide substrates and interacting protein partners is required to understand M1 function in fertility and normal growth and development in plants.

Up-regulation of leucine aminopeptidase-A in cadmium-treated tomato roots

“…LAPs, which are members of the M1 and M17 peptidase families, are metallopeptidases with broad substrate specificity (Matsui et al 2006;Peer 2011). They have been implicated in various processes such as housekeeping proteolysis, cell cycle regulation, transcriptional repression, membrane transporter interaction, wound signaling regulation or stress response (Matsui et al 2006;Peer 2011). In the present study, we focused our attention on LAP response in the roots of Cd-treated tomato plants.…”

M1 aminopeptidases as drug targets: broad applications or therapeutic niche?

“…M1 aminopeptidases exist as monomers and/or dimers (Fig. A,B), are generally membrane bound, and can be found surface‐exposed or within the cytoplasm . The general structure comprises a short tail from the transmembrane anchor/stalk and a large ectodomain with a conserved 3–4 domain fold (Fig.…”

Dictyostelium puromycin-sensitive aminopeptidase A is a nucleoplasmic nucleomorphin-binding protein that relocates to the cytoplasm during mitosis

“…Psa is involved in proteolytic events that mediate processes such as embryogenesis, reproduction, proliferation, meiosis, and establishment of polarity (Brooks et al 2003;Lee and Kim 2009;Lyczak et al 2006;Sanchez-Moran et al 2004). It is also required for proper spermatogenesis, copulatory behavior, and fertility in mice and is thought to regulate the cell cycle via cyclin degradation (Constam et al 1995;Osada et al 2001;Takahashi et al 1989;Peer 2011). Psa is also involved in several human diseases including Alzheimer's disease (AD) and Huntington's disease (HD) (Bhutani et al 2007;Karsten et al 2006;Kudo et al 2011).…”