Biomedical subjects

Natalie A Little

Publications and source records attributed to Natalie A Little.

2 recordsLinked to original sources

PubMed2003

Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2.

The stability of the p53 tumor suppressor protein is critically regulated by the Hdm2 and Hdmx proteins. Hdm2 protein levels are auto-regulated by the self-ubiquitination activity of Hdm2 and on the transcriptional level by p53-activated transcription of the hdm2 gene. Little is known about the regulation of Hdmx expression levels, apart from the observation that the Mdmx protein can be cleaved by caspase-3 in a p53-inducible manner. In the functional analysis of two mutant Hdmx proteins, products of two alternatively spliced mRNAs, it was found that Hdmx proteins are targets for ubiquitination by Mdm2. The stability of the Hdmx protein is partly dependent on the presence of its internal acidic domain. Mdm2 appears only to require an intact RING domain to be able to ubiquitinate Hdmx and target it for proteasomal degradation. These findings highlight the intricate functional relationships between p53, Mdm2, and Hdmx.

Alternative Splicing↗

PubMed2002

p63.

The p63 gene, a member of the p53 gene family, is expressed into at least six protein isoforms which are divided into two groups, those containing the transcription activation domain (TA isoforms) and those that do not (Delta N isoforms). The TA isoforms are similar to p53 in that they are able to activate transcription of specific target genes and induce cell cycle arrest and apoptosis. The Delta N isoforms are unable to activate transcription, and act in a dominant negative manner, inhibiting transcription activation by both p53 and TA isoforms. p63 knock-out studies in mice have shown that p63 plays an important role in development rather than in tumour suppression. In humans, mutations in the p63 gene have been linked with several developmental abnormalities. Studies on human tumours suggest an oncogenic function for Delta N isoforms rather than a tumour suppressor function for the TA forms.

Animals↗