Publication Highlights: Dec 2021/Jan 2022
Translation, a process during protein synthesis, could be a potential target for anti-tumour therapy in colorectal cancer (CRC), as suggested by John Knight and colleagues in their recent study – 'Rpl24Bst mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K'. They investigated an impairment of the protein production machinery, a mutation in the ribosomal subunit Rpl24, in a KRAS- and APC-driven model of CRC - not only did this reduce the overall rate of protein production within tumours, but it also affected tumour growth and development. When studying human tissue, the same signalling pathway, centred around the eEF2 component and its activation, was identified in tumour samples, and hence, its proposed role as a drug-relevant pathway.
Hing Leung, Arnaud Blomme and co-authors have linked the THEM6 protein to drug resistance in advanced prostate cancer ('THEM6-mediated lipid remodelling sustains stress resistance in cancer'). In their study, THEM6 affected the lipid composition of cancer cells, thus altering theirstress response, such as that induced by anti-cancer therapy. As the researchers also observed that THEM6 created a 'tumour stimulating' environment in other hormone-dependent cancers, they propose it as a new therapeutic target beyond just prostate cancer.
The structural complex K48-linked polyUb chain, which fits under the umbrella of ubiquitin (Ub) post-translational modifications, can act as a signal to target proteins for degradation. Using chemical biology approaches, scientists Mark Nakasone and Karolina Majorek described the structure of one of these complexes, consisting of a RING E3, the E2 UBE2K and a Ub acceptor, in Nature Chemical Biology. The study revealed the function – acceptor recognition, multiple Ub binding site or recruitment of Ub substrates- of individual complex components and their domains, and thus, explained the molecular basis of ubiquitin chain assembly, which up till now has remained elusive to the field.
Work by former Beatson PhD student Valentin Barthet and members of the Tumour Cell Death lab characterised two new, but functionally distinct, members of the DRAM protein family, a set of proteins involved in the cell's clean up and recycling function. Unlike other DRAM proteins, p53 did not activate DRAM-4 or DRAM-5, but they were stimulated when nutrient supply was scarce. Although found in distinct locations within the cell, the endosome and plasma, respectively, DRAM-4 and DRAM-5 had compensatory effects on autophagy and cell survival. While these proteins can found in breast cancer cells, further work is required to uncover their exact roles. [DRAM-4 and DRAM-5 are compensatory regulators of autophagy and cell survival in nutrient-deprived conditions in The FEBS Journal]