Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11

Mutations of p53 in cancer can result in a gain of function associated with tumour progression and metastasis. We show that inducible expression of several p53 ‘hotspot’ mutants promote a range of centrosome abnormalities, including centrosome amplification, increased centrosome size and loss of cohesion, which lead to mitotic defects and multinucleation. These mutant p53-expressing cells also show a change in morphology and enhanced invasive capabilities. Consequently, we sought for a means to specifically target the function of mutant p53 in cancer cells. This study has identified ANKRD11 as a key regulator of the oncogenic potential of mutant p53. Loss of ANKRD11 expression with p53 mutation defines breast cancer patients with poor prognosis. ANKRD11 alleviates the mitotic defects driven by mutant p53 and suppresses mutant p53-mediated mesenchymal-like transformation and invasion. Mechanistically, we show that ANKRD11 restores a native conformation to the mutant p53 protein and causes dissociation of the mutant p53–p63 complex. This represents the first evidence of an endogenous protein with the capacity to suppress the oncogenic properties of mutant p53.JE Noll, J Jeffery, F Al-Ejeh, R Kumar, KK Khanna, DF Callen and PM Neilse

YouTube, Migrant Rappers and the Early Cinema Aesthetics: Is There a Digital Public Sphere?

Bringing together contributions from the fields of sociology, media and cultural studies, arts, politics, science and technology studies, political communication theory and popular culture studies, this volume engages both with theoretical debates and detailed empirical studies, showcasing how the public sphere is transformed by digital media, and in turn how this digital public sphere shapes and is shaped by debates surrounding crisis, conflict, migration and culture. Case studies from Bulgaria, Nigeria, China, Greece, Italy, Cyprus, UK, Mexico and India are discussed in detail.1n