The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction

Brooks, Darren R.; Hooper, Nigel M.; Isaac, R. Elwyn

doi:10.1074/jbc.m306216200

Cited by 31 publications

(42 citation statements)

References 62 publications

(60 reference statements)

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“…In Arabidopsis, the single PSA homolog is essential for meiosis (Sanchez-Moran et al, 2004). Less is known about C. elegans PSA, although a previous study showed that PAM-1 is expressed in intestinal cells and in neurons of the head, and in the male tail (Brooks et al, 2003). However, this study did not address maternal, paternal or early embryonic expression, due to germline silencing of the transgene reporter (Brooks et al, 2003).…”

Section: Discussionmentioning

confidence: 53%

“…Less is known about C. elegans PSA, although a previous study showed that PAM-1 is expressed in intestinal cells and in neurons of the head, and in the male tail (Brooks et al, 2003). However, this study did not address maternal, paternal or early embryonic expression, due to germline silencing of the transgene reporter (Brooks et al, 2003). The aminopeptidase activity of C. elegans PAM-1 is similar to other PSA molecules, except that it is less sensitive to puromycin (Brooks et al, 2003).…”

Section: Discussionmentioning

confidence: 77%

“…This protein is highly conserved, being 36-37% identical to human PSA, with key domains showing higher levels of homology (Brooks et al, 2003). PSA is a member of the M1 class of metalloproteases, which cleave N-terminal amino acids from a variety of substrates (Taylor, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…3H,I), but surprisingly some divided asymmetrically with the spindle oriented either toward the posterior (17/54) or toward the anterior (5/54). Brooks et al, 2003). Colored blocks mark amino acid identity.…”

Section: Pam-1 Embryos Lack Early Signs Of Ap Polaritymentioning

confidence: 99%

“…These peptidases are widely conserved and include a human family member (Taylor, 1993). Caenorhabditis elegans has one PSA homolog, PAM-1, a cytoplasmic aminopeptidase localized to neurons and intestinal cells in larvae and adults (Brooks et al, 2003). While PSA has been implicated in cell cycle regulation in mammals, its requirements remain largely unstudied.…”

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confidence: 99%

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The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and anteroposterior polarity in the one-cellCaenorhabditis elegansembryo

et al. 2006

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In the nematode Caenorhabditis elegans, sperm entry into the oocyte triggers the completion of meiosis and the establishment of the embryonic anteroposterior (AP) axis. How the early embryo makes the transition from a meiotic to a mitotic zygote and coordinates cell cycle changes with axis formation remains unclear. We have discovered roles for the C. elegans puromycin-sensitive aminopeptidase PAM-1 in both cell cycle progression and AP axis formation, further implicating proteolytic regulation in these processes. pam-1 mutant embryos exhibit a delay in exit from meiosis: thus, this peptidase is required for progression to mitotic interphase. In addition, the centrosomes associated with the sperm pronucleus fail to closely associate with the posterior cortex in pam-1 mutants,and the AP axis is not specified. The meiotic exit and polarity defects are separable, as inactivation of the B-type cyclin CYB-3 in pam-1mutants rescues the meiotic exit delay but not the polarity defects. Thus PAM-1 may regulate CYB-3 during meiotic exit but presumably targets other protein(s) to regulate polarity. We also show that the pam-1 gene is expressed both maternally and paternally, providing additional evidence that sperm-donated gene products have important roles during early embryogenesis in C. elegans. The degradation of proteins through ubiquitin-mediated proteolysis has been previously shown to regulate the cell cycle and AP axis formation in the C. elegans zygote. Our analysis of PAM-1 requirements shows that a puromycin-sensitive aminopeptidase is also required for proteolytic regulation of the oocyte to embryo transition.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Pam-1 Embryos Lack Early Signs Of Ap Polaritymentioning

confidence: 99%

mentioning

confidence: 99%

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The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and anteroposterior polarity in the one-cellCaenorhabditis elegansembryo

et al. 2006

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Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N

et al. 2015

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Actinonin is a pseudotripeptide that displays a high affinity towards metalloproteases including peptide deformylases (PDFs) and M1 family aminopeptidases. PDF and M1 family aminopeptidases belong to thermolysin-metzincin superfamily. One of the major differences in terms of substrate binding pockets between these families is presence (in M1 aminopeptidases) or absence (in PDFs) of an S1 substrate pocket. The binding mode of actinonin to PDFs has been established previously; however, it is not clear how the actinonin, without a P1 residue, would bind to the M1 aminopeptidases. Here we describe the crystal structure of Escherichia coli aminopeptidase N (ePepN), a model protein of the M1 family aminopeptidases in complex with actinonin. For comparison we have also determined the structure of ePepN in complex with a well-known tetrapeptide inhibitor, amastatin. From the comparison of the actinonin and amastatin ePepN complexes, it is clear that the P1 residue is not critical as long as strong metal chelating head groups, like hydroxamic acid or a-hydroxy ketone, are present. Results from this study will be useful for the design of selective and efficient hydroxamate inhibitors against M1 family aminopeptidases.

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Nematode Aminopeptidases

Brooks

Isaac

2004

Aminopeptidases in Biology and Disease

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The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction

Cited by 31 publications

References 62 publications

The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and anteroposterior polarity in the one-cellCaenorhabditis elegansembryo

The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and anteroposterior polarity in the one-cellCaenorhabditis elegansembryo

Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N

Nematode Aminopeptidases

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