p53 stabilization and functional impairment in the absence of genetic mutation or the alteration of the p14ARF-MDM2 loop in ex vivo and cultured adult T-cell leukemia/lymphoma cells

摘要: Human T-cell lymphotropic virus type I (HTLV-I) transforms T cells in vitro, and the viral transactivator Tax functionally impairs tumor suppressor p53 protein, which is also stabilized HTLV-I–infected cells. Thus, functional impairment of essential to maintain viral-induced proliferation CD4+ mature However, leukemic patients with adult leukemia/lymphoma (ATLL), does not appear be expressed, mutations have been found only a fraction patients. We sought investigate whether function impaired, ex vivo samples from ATLL, absence genetic mutations. Here we demonstrate that protein ATLL (10 10 studied) at least 2 stabilization was associated mutation. Furthermore, assessment after ionizing radiation indicated an abnormal induction p53-responsive genes GADD45 p21WAF1 7 In patients, regulation cell-cycle progression appeared impaired as well. Because part regulatory loop involves MDM2 p14ARF, status latter proteins assessed cultured or fresh The p97 detected by Western blot analysis established lines cell lysates. could easily treatment specific proteasome inhibitor lactacystin, suggesting normal p53–MDM2 regulating loop. Similarly, p14ARF did aberrantly expressed nor any studied. HTLV-I infection occurs mutation alteration physiologic degradation pathway p53.