The Octapeptide (Fragment of Differentiation Factor HLDF) Exhibits Nuclease Activity and Induces Apoptosis

Previously, we isolated the differentiation factor HLDF of 8.2 kDa molecular mass from the culture medium of the promyelocyte human leukemia cells (HL-60) treated with all-E-retinoic acid and characterized it as the factor differentiating these cells into granulocytes [1]. A search in the EMBL computer database (www.embl-heidelberg.de) revealed a significant homology between the cDNA sequence of the differentiation factor and that of the S21 ribosomal protein [2]. However, no homology was observed between the primary structures of the mature proteins, since two nucleotides, G in position 112 and C in position 224, in the cDNA of RPS21 are deleted from that of the HLDF precursor. As a result of these point mutations, the mature differentiation factor and the S21 ribosomal protein were the translation products from different reading frames. In earlier studies, we have shown that the hexapeptide fragment of the HLDF: TGENHR (HLDF-6) fully reproduces the differentiating and antiproliferative activities of the native HLDF in experiments on the HL-60 cells. It was also found using a model of transplantable NSO myeloma that HLDF-6 has antitumor activity [3]. This study is devoted to the identification and the structure-function analysis of the HLDF fragment that exhibits DNA/RNA-hydrolyzing activity.