Matrin 3 is a Ca2+/calmodulin-binding protein cleaved by caspases.
Matrin 3 is a nuclear matrix protein that has been implicated in interacting with other nuclear proteins to anchor hyperedited RNAs to the nuclear matrix, in modulating the activity of proximal promoters, and as the main PKA substrate following NMDA receptor activation. In our proteome-wide selections for calmodulin (CaM) binding proteins and for caspase substrates using mRNA-displayed human proteome libraries, matrin 3 was identified as both a Ca(2+)-dependent CaM-binding protein and a downstream substrate of caspases. We report here, the in vitro characterization of the CaM-binding motif and the caspase cleavage site on matrin 3. Significantly, the Ca(2+)/CaM-binding motif is partially overlapped by the RRM of matrin 3 and is also very close to the bipartite NLS that is essential for its nuclear localization. The caspase cleavage site is downstream of the NLS but upstream of the second U1-like zinc finger. Our results suggest that the functions of matrin 3 could be regulated by both Ca(2+)-dependent interaction with CaM and caspase-mediated cleavage.
School of Pharmacy and Carolina Center for Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
C Alexander
CA
Valencia
Wujian
W
Ju
Rihe
R
Liu
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019921:Biotinylation; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012685:Sepharose / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors
D002148:Calmodulin-Binding Proteins; C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D020543:Proteome; D016601:RNA-Binding Proteins; D012685:Sepharose; D053148:Caspase 3; D020169:Caspases; D002118:Calcium