Analysis of Apoptosis Induced by HIV-1 Vpr and Examination of the Possible Role of the hHR23A Protein

Molecular mimicry in inducing DNA damage between HIV-1 Vpr and the anticancer agent, cisplatin

“…In other studies, induction of apoptosis by Vpr was attributed to rapid dissipation of the mitochondrial transmembrane potential, association of Vpr with the adenine nucleotide translocator, release of cytochrome c and activation of caspase-3 (Jacotot et al, 2000). Finally, Vpr-induced apoptosis has been shown to require the activation of caspase-8 (Patel et al, 2000), and be part of a pathway involving hHR23A (Gaynor and Chen, 2001). Vpr was also shown to induce cell death in rat astrocytes primarily by a necrotic mechanism (Huang et al, 2000).…”

Mutational analysis of growth arrest and cellular localization of human immunodeficiency virus type 1 Vpr in the budding yeast, Saccharomyces cerevisiae

“…The C-terminal region of Vpr has been shown to be important for this activity, because C-terminal deletion, as well as point mutations in the C-terminus (H71R, R73A, I74P, G75A, C76A, R80A, and R90K), have been demonstrated to cancel or strongly reduce such activity Gaynor and Chen, 2001;Mahalingam et al, 1997;Mansky et al, 2001;Nishizawa et al, 1999;Selig et al, 1997;Vodicka et al, 1998). In addition, a point mutation of the N-terminal region, A30L Gaynor and Chen, 2001;Mahalingam et al, 1997), is also known to cancel this activity.…”

“…The C-terminal region of Vpr has been shown to be important for this activity, because C-terminal deletion, as well as point mutations in the C-terminus (H71R, R73A, I74P, G75A, C76A, R80A, and R90K), have been demonstrated to cancel or strongly reduce such activity Gaynor and Chen, 2001;Mahalingam et al, 1997;Mansky et al, 2001;Nishizawa et al, 1999;Selig et al, 1997;Vodicka et al, 1998). In addition, a point mutation of the N-terminal region, A30L Gaynor and Chen, 2001;Mahalingam et al, 1997), is also known to cancel this activity. For the nuclear localization of Vpr, both the N-terminal region and the C-terminus are considered to be important, because E25K, H71R, and C-terminal deletion mutants have all been shown to change the localization of Vpr from the nucleus to the cytoplasm in mammalian cells (Lu et al, 1993;Mahalingam et al, 1997;Vodicka et al, 1998;Yao et al, 1995).…”

“…Several domains in Vpr appear to be involved in this activity, because mutations in the N-terminus (Q3R), in the middle region (L67A), and in the C-terminus (I74P, C76A, and R80A) cancel or reduce apoptosis-inducing activity (Gaynor and Chen, 2001;Nishizawa et al, 2000;Somasundaran et al, 2002). Vpr is known to bind UNG, which is involved in DNA repair and in the DNA damage checkpoint activation process .…”

“…By expressing point-mutated Vpr in mammalian cells, several regions including these helices are shown to be important for virion incorporation, G2 arresting activity, and the nuclear localization of Vpr Di Marzio et al, 1995;Gaynor and Chen, 2001;Mahalingam et al, 1995;Singh et al, 2000). However, these regions appear to act independently of each other, since G2 arrest by Vpr is not dependent on nuclear accumulation, nor on virion incorporation in mammalian cells Yao et al, 1995).…”