SAM domain-containing N-terminal region of SAMHD1 plays a crucial role in its stabilization and restriction of HIV-1 infection
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SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) infection in a cell-type specific manner. Other than primarymonocyte derived cells and resting CD4<sup>+</sup> T cells, the SAMHD1-mediated HIV-1 block was reported only in phorbol12-myristate 13-acetate (PMA)-differentiated THP-1 and U937 monocyte cell lines. We previously reported that SAMHD1restricted HIV-1 infection in TE671 rhabdomyosarcoma cells in addition to these cell lines. In this study, we compared theamounts of the full-length SAMHD1 and its deletion mutants, SAM domain containing N-terminal fragment (residues 1-119,SAMHD1n) and HD domain containing C-terminal fragment (120-626, SAMHD1c) in U937, TE671, and HeLa cells. The resultsshowed that the full-length SAMHD1 and SAMHD1n proteins were significantly more abundant than the SAMHD1c proteinin TE671 and differentiated U937 cells. The proteasome inhibitor MG132 increased the amount of the SAMHD1c and theSAMHD1c-fused GFP proteins. In contrast, the fusion of the SAMHD1n to the APOBEC3G protein inhibited Vif-induced proteasomaldegradation in TE671 and in differentiated U937 cells. These results indicated that the SAMHD1 C-terminal HDdomain-containing region leads the SAMHD1 to proteasomal degradation, and the SAMHD1 N-terminal SAM domain-containingregion stabilizes the protein. Our study showed that the SAMHD1 protein expression is post-translationally regulatedand the significance of SAM and HD domains for the full-length SAMHD1 protein stability. Further, we suggest that the SAMdomain-containing N-terminal region participate in the cell-type specific restrictive function of SAMHD1 against HIV-1 infection,by protein stabilization.
- Acta Medica Nagasakiensia
Acta Medica Nagasakiensia 58(4), 103-111, 2014
Nagasaki University School of Medicine