Retinoic acid regulates aberrant nuclear localization of PML-RARα in acute promyelocytic leukemia cells

SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

“…Interestingly, most so far known interaction partners of E1B-55K are transient components of the nuclear promyelocytic leukaemia (PML) bodies (Van Damme et al, 2010). The PML protein has first been described as the causal agent in acute promyelocytic leukaemia as a fusion with the RARa receptor generated by the chromosomal translocation t(15;17) (Ascoli and Maul, 1991;de The et al, 1991;Kakizuka et al, 1991;Chang et al, 1992;Goddard et al, 1992;Kastner et al, 1992;Pandolfi et al, 1992;Dyck et al, 1994;Koken et al, 1994;Weis et al, 1994;Melnick and Licht, 1999;. Since these initial findings, it has become evident that PML is a general tumour suppressor frequently deregulated in various tumour types (Gurrieri et al, 2004) most presumably involving secondary effects of PML bodies as sites of protein degradation (Lallemand-Breitenbach et al, 2001), transcriptional regulation (Li et al, 2000;Zhong et al, 2000), cellular senescence (Ferbeyre et al, 2000;Pearson et al, 2000;Bischof et al, 2002;Langley et al, 2002), tumour suppression (Salomoni and Pandolfi, 2002;Salomoni et al, 2008), DNA repair (Bischof et al, 2001;Carbone et al, 2002), apoptosis (Hofmann and Will, 2003;Takahashi et al, 2004) and epigenetic regulation (Torok et al, 2009).…”

Body language: the function of PML nuclear bodies in apoptosis regulation

“…2 Under normal growth conditions, almost every mammalian cell usually harbours between 10 and 30 doughnut-like-shaped PMLNBs with a diameter ranging between 0.2 and 1 mm. [3][4][5][6][7] Besides a number of viral proteins, to date more than 40 different cellular proteins have been found in association with PML-NBs ( Figure 1). Although the molecular function of PMLNBs is currently not clear, there is accumulating evidence that PML-NBs are regulatory domains involved in various biological processes, including protein degradation, 5 transcriptional regulation, 8,9 cell growth, 10,11 antiviral response, 12,13 cellular senescence, [14][15][16][17] tumour suppression, 18 DNA repair 19,20 and apoptosis.…”

Formation of PML/RARα high molecular weight nuclear complexes through the PML coiled-coil region is essential for the PML/RARα-mediated retinoic acid response

“…It has been proposed that PML/RARa exerted a dominant negative action on the function of the corresponding wild-type PML and RARa proteins (Dyck et al, 1994;Weis et al, 1994;Koken et al, 1994). This hypothesis was based on transactivation experiments, showing a dominant negative activity of PML/RARa on RARa (Kakizuka et al, 1991;De The et al, 1991;Pandol® et al, 1991;Kastner et al, 1992), and on the nuclear localization pattern of these proteins.…”

“…This hypothesis was based on transactivation experiments, showing a dominant negative activity of PML/RARa on RARa (Kakizuka et al, 1991;De The et al, 1991;Pandol® et al, 1991;Kastner et al, 1992), and on the nuclear localization pattern of these proteins. RARa is nuclear di use (Gaub et al, 1989), PML is localized within speci®c subnuclear structures called PML nuclear bodies, while PML/RARa has distinct distribution pattern (microspeckled localization) (Dyck et al, 1994;Weis et al, 1994;Koken et al, 1994;Flenghi et al, 1995). Expression of PML/RARa produces delocalization within microspeckles of PML and RXR, an RARa cofactor (Chambon, 1996), and so might alter the function of both PML and RARa.…”