Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors.

Abstract

(ii) it is found in a tumor previously not thought to be affected by p53 alteration.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…This phenotype was present in 37% of in¯ammatory breast carcinomas and greater than 95% of undifferentiated neuroblastomas but never in di erentiated benign derivatives of NB (Moll et al, 1992(Moll et al, , 1995(Moll et al, , 1996. This naturally occurring translocation defect compromises the suppressor function of p53 and likely plays a role in the tumorigenesis of these tumours previously thought to be una ected by p53 alterations.…”

K-ras modulates the cell cycle via both positive and negative regulatory pathways

“…These additional mechanisms include stability of the protein (Bae et al, 1995), sequestration in the cytoplasm (Moll et al, 1995), tetramer formation (Friedman et al, 1993) and phosphorylation (Meek and Eckhart, 1988). Therefore, it was necessary to determine if the induced p53 protein correlated with p53-mediated transactivation.…”

Cyclooxygenase inhibitors modulate the p53/HDM2 pathway and enhance chemotherapy-induced apoptosis in neuroblastoma

“…Although p53 is mutated in over 50% of tumors, p53 mutations are rarely present in de novo neuroblastoma (Imamura et al, 1993;Komuro et al, 1993;Vogan et al, 1993;Hosoi et al, 1994). However, wild-type p53 is inactivated in some neuroblastoma via various mechanisms including p53 cytoplasmic sequestration (Moll et al, 1995;Tweddle et al, 2001), HDM2 amplification (Corvi et al, 1995), inactivation of p14 ARF (Carr et al, 2006), and overexpression of Twist (Valsesia-Wittmann et al, 2004). Cellular levels of p53 are low under normal conditions and are tightly regulated by one of p53's own target gene products HDM2, an E3 ubiquitin ligase for p53, which in turn can be modulated by p14 ARF .…”