E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating
transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to substrate. The activity of …

Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen,
the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 …

Malignant astrocytic gliomas such as glioblastoma are the most common and lethal
intracranial tumors. These cancers exhibit a relentless malignant progression characterized …

The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many
human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour …

The traditional view of p53 activation includes three steps—p53 stabilization, DNA binding,
and transcriptional activation. However, recent studies indicate that each step of p53 …

Covalent attachment (conjugation) of one or more ubiquitin molecules to protein substrates
governs numerous eukaryotic cellular processes, including apoptosis, cell division and …

Mutations in TP53, the gene that encodes the tumour suppressor p53, are found in 50% of
human cancers, and increased levels of its negative regulators MDM2 and MDM4 (also …

The cellular response to external stress signals and DNA damage depends on the activity of
ubiquitin ligases (E3s), which regulate numerous cellular processes, including homeostasis …

Currently, around 11 million people are living with a tumour that contains an inactivating
mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours …

Purpose: We describe the first-in-human dose-escalation trial for ALRN-6924, a stabilized,
cell-permeating peptide that disrupts p53 inhibition by mouse double minute 2 (MDM2) and …