The HTLV-1 tax oncoprotein attenuates DNA damage induced G1 arrest and enhances apoptosis in p53 null cells

Virology. 2003 Jan 20;305(2):229-39. doi: 10.1006/viro.2002.1642.


Transformation of cells by the human T cell leukemia virus type 1 occurs via mechanisms unique among oncogenic retroviruses. A prevailing hypothesis for HTLV-1-mediated cellular transformation is that expression of the viral transactivator, Tax, induces genomic instability. Tax-mediated failure in the cellular repair response is one possible mechanism for loss in genomic integrity. Here we have examined the in vivo repair response of Tax-expressing cells to determine the underlying defects that contribute to loss of genomic integrity. In these studies we examined the effects of de novo Tax-expression in naive "pre-neoplastic" REF52 cells. DNA-damage-induced p53 stabilization and concomitant transient stabilization of p21 were clearly evident in Tax-expressing cells. Likewise, the damage-induced apoptotic response of Tax-expressing cells was normal. However, the damage-induced G1 checkpoint was abrogated in either p53+ or p53- cellular backgrounds. Although nucleotide excision repair (NER) of asynchronous Tax-expressing cells was impaired, cell-cycle-independent assessment of NER in the global excision repair assay demonstrated comparable NER activity in Tax-expressing cells, suggesting that the failure of G1 checkpoint contributes to NER deficiency. Interestingly, we observed a dramatic increase in apoptosis and UV sensitivity of Tax-expressing p53-/- cells when compared to Tax-expressing p53+/+ cells. These data demonstrate that Tax-mediated cellular genomic instability arises from attenuation of cell-cycle checkpoint and imply a clonal dependence on p53 status separate from genomic integrity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis*
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis
  • DNA Damage*
  • DNA Repair
  • G1 Phase / physiology*
  • Gene Products, tax / physiology*
  • Humans
  • Tumor Suppressor Protein p53 / physiology*
  • Ultraviolet Rays


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Gene Products, tax
  • Tumor Suppressor Protein p53