Fig. 8
Regulation of SAMHD1 T592 phosphorylation in cycling and differentiated cells. a Regulation of SAMHD1 T592 phosphorylation in cycling cells. Initially, phosphorylation at T592 in SAMHD1 is introduced by CDK2/cyclin A2 in S phase and maintained by CDK1/cyclin A2 until mitosis. SAMHD1 T592 phosphorylation is rapidly lost upon G1 entry, more specifically during mitotic exit, through dephosphorylation by PP2A-B55α holoenzymes. Dephosphorylated SAMHD1 can reduce or delay viral cDNA synthesis upon HIV-infection in the G1 stage—even in cycling cells. b Regulation of SAMHD1 T592 phosphorylation in differentiated MDMs. Control of T592 phosphorylation level in SAMHD1 is exerted through differential CDK1/2 activities, potentially depending on the macrophage type. Furthermore, PP2A-B55α holoenzymes are involved in balancing SAMHD1 T592 phosphorylation in differentiated MDMs. IFN leads to upregulation of PP2A B55α subunit, an additional layer of regulation to control SAMHD1 antiviral activity
