The evolutionarily conserved Dim1 protein defines a novel branch of the thioredoxin fold superfamily.
Dim1 is a small evolutionarily conserved protein essential for G2/M transition that has recently been implicated as a component of the mRNA splicing machinery. To date, the mechanism of Dim1 function remains poorly defined, in part because of the absence of informative sequence homologies between Dim1 and other functionally defined proteins or protein domains. We have used a combination of molecular modeling and NMR structural analysis to demonstrate that approximately 125 of the 142 amino acids of human Dim1 (hDim1) define a novel branch of the thioredoxin fold superfamily. Mutational analysis of Dim1 based on the predicted fold indicates that alterations in the region corresponding to the thioredoxin active site do not affect Dim1 activity. However, removal of a very short carboxy-terminal extension generates a dominant negative form of the protein [hDim1-(1-128)] that when overproduced induces cell cycle arrest in G2, via a mechanism likely to involve alteration of Dim1 association with partner molecules. In sum, this study identifies the Dim1 proteins as a novel sixth branch of the thioredoxin superfamily involved in cell cycle.
Zhang
Y Z
YZ
Division of Basic Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Gould
K L
KL
Dunbrack RL
J R
JR
Cheng
H
H
Roder
H
H
Golemis
E A
EA
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D017124:Conserved Sequence; D004274:DNA, Recombinant / Q000235:genetics; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D016195:G2 Phase; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry* / Q000235:genetics; D014162:Transfection; D014170:Transformation, Genetic
D018797:Cell Cycle Proteins; D004274:DNA, Recombinant; D005656:Fungal Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; C118369:dim1 protein, S pombe; D049452:Green Fluorescent Proteins; D013879:Thioredoxins