Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.
C19ORF5 is a homologue of microtubule-associated protein MAP1B that interacts with natural paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Although normally distributed throughout the cytosol, C19ORF5 specifically associates with microtubules stabilized by paclitaxel or RASSF1A. At sufficiently high concentrations, C19ORF5 causes mitochondrial aggregation and genome destruction (MAGD). The accumulation on hyperstabilized microtubules coupled to MAGD has been proposed to mediate tumor suppression by the taxoid drug family and RASSF1A. Here, we show that the C-terminus of C19ORF5 (C19ORF5C) interacts with mitochondria-associated DNA binding protein, LRPPRC, in liver cells. Like LRPPRC, C19ORF5 also binds DNA with an affinity and specificity sufficient to be of utility in DNA affinity chromatography to purify homogeneous recombinant C19ORF5C from bacterial extracts. Homogeneous C19ORF5 exhibited no intrinsic DNase activity. Deletion mutagenesis indicated that C19ORF5 selectively binds double stranded DNA through its microtubule binding domain. These results suggest C19ORF5 as a DNA binding protein similar to microtubule-associated proteins tau and MAP2.
Liu
Leyuan
L
Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030-3303, USA.
Vo
Amy
A
Liu
Guoqin
G
McKeehan
Wallace L
WL
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C087940:LRPPRC protein, human; C475491:MAP1B protein, human; C493240:MAP1S protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C411762:RASSF1 protein, human; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA