Neoplastic transformation requires the elimination of key tumor suppressors, which may result from E3 ligase-mediated proteasomal degradation. We previously demonstrated a key role for the E3 ubiquitin ligase E6AP in the regulation of promyelocytic leukemia protein (PML) stability and formation of PML nuclear bodies. Here, we report the involvement of the E6AP-PML axis in B-cell lymphoma develo...

The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells...

BACKGROUND Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS Patients from ...

Disaggregation of the spherical nuclear bodies termed promyelocytic (PML) oncogenic domains (PODs) is a characteristic of acute promyelocytic leukemia. Here, we demonstrate that the cAMP enhancer binding protein (CREB)-binding protein (CBP) associates with PML in vitro and is recruited to the PODs in vivo. Through its association with CBP, wild-type PML dramatically stimulates nuclear receptor ...

Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) is the first example of targeted therapy. In fact, the oncogenic fusion-protein (PML-RAR) typical of this leukemia contains the retinoid-nuclear-receptor RARα. PML-RAR is responsible for the differentiation block of the leukemic blast. Besides PML-RAR, two endogenous RARα proteins are present in APL blasts, i.e....

Post-translational modification by small ubiquitin-like modifier (SUMO) plays an important role in the regulation of different signaling pathways and is involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies following sumoylation of PML. In the present study, we found that IL-6 induces desumoylation of PML and dissociation between PML and SUMO1 in hepatoma cells. We al...

The PML protein induces senescence, and, upon oncogenic stress, its absence promotes cellular transformation. In this issue of Cell, Scaglioni et al. (2006) show that phosphorylation of PML by CK2, a kinase frequently activated in human cancers, promotes PML degradation. Therefore, pharmacological inhibition of CK2-induced PML loss could be used to offset tumor establishment.

Mutations in the p53 tumor suppressor are the most common genetic events in human cancer. These mutations not only result in a loss of wild-type p53 activity, but can also lead to a gain of new oncogenic properties. Understanding how these gained functions are regulated is in its infancy. In this study, we show that the promyelocytic leukemia (PML) protein is an important regulator of mutant p5...

Artificial boundaries are necessary in seismic numerical modeling to constrain the computational limits. Special treatment is necessary to reduce spurious reflections from these artificial boundaries. For near-surface seismic modeling, boundary processing is particularly important due to the presence of surface waves. The Perfectly Matched Layer (PML) method is an efficient way of attenuating b...