Several ubiquitin-like proteins recently discovered have been confirmed to modify proteins akin to ubiquitinization for fineregulation of intracellular proteins. In the present study, we report a novel ubiquitin-like protein from human dendritic cells (DC), named as dendritic cell-derived ubiquitin-like protein (DC-UbP). The full-length of DC-UbP cDNA is 565 bp and encodes 106 amino acids. Ubiquitin domain (UBQ) in DC-UbP shares 28.6% identity and 55% similarity to ubiquitin, but does not possess the conserved C-terminus Gly-Gly of ubiquitin required for ubiquitinization. DC-UbP localized in cytoplasm, especially in mitochondrion, indicating that it may play a role in mitochondrial biology. DC-UbP mRNA was expressed in various tumor cells, but not in adult human normal tissues, suggesting that DC-UbP might be related to tumor genesis. In addition, DC-UbP mRNA expression decreased in the HL60 cells undergoing apoptosis after being stimulated with TRAIL and in the differentiated HL60 cells induced by ARTA. Taken together, DC-UbP might be downregulated during cellular differentiation and apoptosis.