The MPAC domain is a novel mitotically regulated domain, removed by apoptotic protease cleavage during cell death.
The apoptotic proteases, including caspases and granzyme B, have independent evolutionary origins, yet are both highly specific for cleavage after aspartic acid residues and cleave many of the same substrates at closely spaced sites. In addition, many of these substrates are also reversibly regulated during other processes such as the cell cycle. In these studies, we have identified a novel domain (the MPAC domain: Mitotically Phosphorylated, Apoptotically Cleaved) present at the N-terminus of Ufd2a, which is regulated both by cleavage during cell death, and by phosphorylation during mitosis. We have also identified a corresponding domain, at the C-terminus of polyA polymerase (PAP), which is similarly regulated by phosphorylation during mitosis and is delineated by an apoptotic protease cleavage site. The positioning of the apoptotic cleavage site suggests that it represents a novel connector between the regulatory domain and its functional partner(s), providing insights into the structure and function that guided the evolution of the apoptotic proteases.
Spinette
Sarah
S
Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA.
Mahoney
James A
JA
Rosen
Antony
A
D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism; D053804:Granzymes; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D025521:Tumor Suppressor Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C473697:UBE4B protein, human; D044767:Ubiquitin-Protein Ligases; D016203:CDC2 Protein Kinase; D011062:Polynucleotide Adenylyltransferase; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases