The differentiation and activation of monocytes (MO) and monocytic cells is modulated by 1alpha,25-dihydroxyvitamin D3 (Vitamin D3). Recently, using mRNA Differential Display technology, Fritsche J, et al have identified a gene which is induced in freshly isolated human blood MO that are cultured for 4 hours with Vitamin D3 (1). This cDNA encodes a putative 16.5 kD protein. The product of this gene has structural homology with yeast MMS2p and human CROC-1), which defines a structurally and functionally conserved Ubc-like protein family (2). This protein was called Ubiquitin E2 variant (UBE2V2) or MMS2 (methyl methanesulfonate sensitive 2). The yeast UEV protein, Mms2, is required together with Ubc13 for RAD6/RAD18-dependent postreplicative DNA repair in yeast (3). These proteins also play a central role in the assembly of K63-linked polyubiquitin chains (4,5) UEV/Ubc complexes have been implicated in the assembly of Lys63-linked polyubiquitin chains that act as a novel signal in postreplicative DNA repair and IkBa kinase activation. Recent crystal structure analysis provides direct evidence that the Mms2/Ubc13 heterodimer is necessary for DNA repair (6,7).
1 alpha,25-dihydroxyvitamin D3-inducible; DDVit 1; EDAF-1; EDPF-1; enterocyte differentiation promoting factor; Enterocyte differentiation-associated factor 1; enterocyte differentiation-associated factor EDAF-1; Enterocyte differentiation-promoting factor 1; methyl methanesulfonate sensitive 2; methyl methanesulfonate sensitive 2, S. cerevisiae, homolog of; MMS2 homolog; Ubc-like protein MMS2; ubiquitin conjugating enzyme E2 variant 2; Ubiquitin-conjugating enzyme E2 variant 2; Vitamin D3-inducible protein