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Polyomavirus Small t Antigen Prevents Retinoic Acid-Induced Retinoblastoma Protein Hypophosphorylation and Redirects Retinoic Acid-Induced G(0) Arrest and Differentiation to Apoptosis

By Andrew Yen, Lisa Placanica, Stephen Bloom and Susi Varvayanis


Polyomavirus small t antigen (ST) impedes late features of retinoic acid (RA)-induced HL-60 myeloid differentiation as well as growth arrest, causing apoptosis instead. HL-60 cells were stably transfected with ST. ST slowed the cell cycle, retarding G(2)/M in particular. Treated with RA, the ST transfectants continued to proliferate and underwent apoptosis. ST also impeded the normally RA-induced hypophosphorylation of the retinoblastoma tumor suppressor protein consistent with failure of the cells to arrest growth. The RA-treated transfectants expressed CD11b, an early cell surface differentiation marker, but inducible oxidative metabolism, a later and more mature functional differentiation marker, was largely inhibited. Instead, the cells underwent apoptosis. ST affected significant known components of RA signaling that result in G(0) growth arrest and differentiation in wild-type HL-60. ST increased the basal amount of activated ERK2, which normally increases when wild-type cells are treated with RA. ST caused increased RARĪ± expression, which is normally down regulated in RA-treated wild-type cells. The effects of ST on RA-induced myeloid differentiation did not extend to monocytic differentiation and G(0) arrest induced by 1,25-dihydroxy vitamin D(3), whose receptor is also a member of the steroid-thyroid hormone superfamily. In this case, ST abolished the usually induced G(0) arrest and retarded, but did not block, differentiation without inducing apoptosis, thus uncoupling growth arrest and differentiation. In sum, the data show that ST disrupted the normal RA-induced program of G(0) arrest and differentiation, causing the cells to abort differentiation and undergo apoptosis

Topics: Virus-Cell Interactions
Publisher: American Society for Microbiology
Year: 2001
DOI identifier: 10.1128/JVI.75.11.5302-5314.2001
OAI identifier:
Provided by: PubMed Central
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