Human T-lymphotropic virus proteins and post-translational modification pathways

Figure 2 Cell cycle deregulation in infected cells and Tax-expressing cells. G1 progression begins with cyclin D expression, formation of the Cdk4/cyclin D complex that in turn phosphorylates retinoblastoma protein (Rb), inducting E2F1 transcription. Cyclin D is upregulated by Tax and by Ras-Raf-ERK stimulation. It is stabilized by interaction with Pin1, overexpressed in infected cells. G1/S phase transition, promoted by the Cdk2/cylclin E complex is antagonized by p30 and by overexpressed p27/Kip1. Overexpressed p21/Waf1 inhibits Cdk2/cyclin A-promoted S/G2 transition. In turn, overactivation of Akt inhibits p27/Kip1 and p21/Waf1 functions. Tax promotes, through cdc20-associated anaphase promoting complex (Cdc20-APC) activation, cyclin B degradation. At the same level acts p30, that activates Cdk1 by Cdc25-dependent de-phosphorylation. Cyclic stability of Cdk/cyclin complexes are represented with fading arcs; P: Phosphorylation; Ub: Ubiquitin; black thin arrows represent activation, grey thin arrows represent enzymatic reactions; protein overexpression in infected cells is represented by thick straight arrows.