Murine Coronavirus Replication Induces Cell Cycle Arrest in G₀/G₁Phase

Abstract

Mouse hepatitis virus (MHV) replication in actively growingMany DNA viruses usurp host cell cycle regulation for their own replication advantage (reviewed in reference 56). Small DNA tumor viruses, such as simian virus 40 (13, 22), adenovirus (18, 36), and human papillomavirus (75, 79), encode proteins that promote cells to enter the S phase. In contrast, herpesviruses, a group of large DNA viruses that encode their own DNA polymerases, generally block cell cycle progression at the G 0 /G 1 phase during lytic infection cycles (reviewed in reference 25). Studies of cell cycle dysregulation induced by RNA viruses have been relatively limited. That reovirus infection causes the inhibition of cellular DNA synthesis has been known for some time (12,20,30), but not until more recently was it shown that reovirus-induced inhibition of cell proliferation results from G 2 /M cell cycle arrest that is mediated by the viral 1s nonstructural protein (59). Human immunodeficiency virus type 1 infection also induces cell cycle arrest in the G 2 /M phase (32), and the expression of the accessory gene product Vpr alone is sufficient for inducing G 2 /M cell cycle arrest (60, 62). Vpr-mediated cell cycle arrest apparently favors virus replication, since the long terminal repeat is most active and the expression of the viral genome is optimal in the G 2 phase of the cell cycle (27). Cell cycle perturbations have also been seen in cells infected with the paramyxovirus simian virus 5 (44), measles virus (49,50,53), and coxsackievirus (48).Cyclins and cyclin-dependent kinases (Cdks) form complexes and play important regulatory roles in controlling cell cycle progression (reviewed in references 55 and 58). G 1 -phase progression requires the activities of cyclin D-Cdk4/6 complexes, and cyclin E-Cdk2 activity is necessary for the G 1 /Sphase transition. These G 1 cyclin-Cdk complexes regulate the cell cycle through phosphorylation of the retinoblastoma protein (pRb) p107 and pRB family proteins and p130. In the quiescent G 0 phase, pRb is nonphosphorylated, while during the G 1 phase, it is sequentially hypophosphorylated by cyclin D-Cdk4/6 complexes in early G 1 and hyperphosphorylated by the cyclin E-Cdk2 complex in late G 1 (47). It remains hyperphosphorylated in the S, G 2 , and M phases of cycling cells (14). When pRb binds to the E2F family of transcription factors, it functions as a transcriptional repressor, and its hyperphosphorylation in late G 1 results in inactivation, release of E2F, and transcription of genes important for DNA synthesis (reviewed in references 17 and 31).The activities of G 1 cyclin-Cdk complexes are regulated by cellular Cdk inhibitors (CKIs) (reviewed in reference 65). INK4 family CKIs bind to Cdk4 and Cdk6, thus blocking cyclin D-Cdk4/6 activities (reviewed in references 63 and 64). CKIs of the Cip/Kip family, including p21Cip1 , p27 Kip1 , and p57 Kip2 , are potent inhibitors of cyclin E-and A-dependent Cdk2 (reviewed in reference 51). The regulation of G 1 cyclin quantities is also important for prop...

Sleeping Beauty Transposition

“…Other parasitic genetic elements, including HIV-1 (108), Herpes simplex virus (109), cytomegalovirus (110), Epstein-Barr virus (111), Kaposi's sarcoma-associated herpesvirus (112), and mouse hepatitis virus (113), have also developed versatile strategies to perturb the cellular machinery to maximize their chance for survival and propagation. Thus, overriding the normal cell-cycle program seems to be a shared strategy of parasitic genetic elements.…”

Furanodiene, a Natural Product, Inhibits Breast Cancer Growth Bothin vitroandin vivo

“…These G1 cyclin-Cdk complexes regulate the cell cycle through the phosphorylation of the retinoblastoma protein (pRb) p107 and pRb family proteins and p130. In the quiescent G0 phase, pRb is nonphosphorylated, whereas in the early G1 phase and late G1 phase, it is sequentially hypophosphorylated and hyperphosphorylated by cyclin D-Cdk4/6 complexes and cyclin E-Cdk2 complex, respectively [30]. Therefore, the reduction of the G1 phase cell cycle-related proteins of p-cyclinD1, cyclin D1, p-CDK2, CDK2, Rb, and pRb by furanodiene might account for the G0/G1 phase arrest.…”

Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1

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