Short, accessible synopses of recent important articles concerning signalling pathways.
SRC is a non-receptor tyrosine kinase that is involved in regulating many important cellular processes. Needless to say its activity is tightly controlled, as once overexpressed it is able to transform cells. As has been investigated for other oncogenes recently, George Laszlo and Jonathan Cooper have examined how much SRC is too much SRC. Their answer indicates that this depends on whether the ubiquitin ligase cullin 5 (CUL5) is expressed.
Original research paper Nature Reviews Cancer 9 9 148 - 149 doi:10.1038/nrc2611
How mechanical force results in a chemical response is poorly understood. Two papers in Science provide new insights into the mechanisms that underlie the activation of the adhesion receptor 51 integrin (51) by mechanical force and the interaction of the force-bearing cytoskeleton protein talin with its binding partner, vinculin.
Original research paper Nature Reviews Molecular Cell Biology 10 10 163 doi:10.1038/nrm2642
The mitotic checkpoint is a surveillance mechanism that delays the onset of anaphase until all chromosomes are properly attached to the spindle microtubules. A checkpoint-induced 'wait anaphase' signal prevents cell division cycle 20 (CDC20) from activating the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which promotes the degradation of proteins that arrest the cell cycle. But what is the molecular basis for this signal? Two studies in Developmental Cell provide new clues.
Original research paper Nature Reviews Molecular Cell Biology 10 10 160 - 161 doi:10.1038/nrm2643
The ubiquitin system regulates the function of proteins by conjugating different types of polyubiquitin chains. Non-linear Lys48-linked polyubiquitin chains (in which the carboxyl group of ubiquitin is linked to a Lys side chain of another ubiquitin) serve as signals for degradation by the 26S proteasome, whereas non-linear Lys63-linked polyubiquitin chains function in DNA damage and cellular signalling. Now, Kazuhiro Iwai and co-workers show that a new type of in vivo ubiquitin chain, head-to-tail-linked linear polyubiquitin (in which the C terminus of ubiquitin is conjugated to the amino terminus of another ubiquitin), activates the canonical nuclear factor-B (NF-B) pathway.
Original research paper Nature Reviews Molecular Cell Biology 10 10 162 doi:10.1038/nrm2638
The idea that the precursor of brain-derived neurotrophic factor (BDNF), proBDNF, can itself affect neuronal survival and function has spurred a flurry of research in this area. However, whether and under what circumstances proBDNF is secreted by neurons remain unclear, particularly as a recent study by Matsumoto et al. demonstrated efficient intracellular cleavage to mature BDNF in cultured neurons. Two new papers support the concept of neuronal proBDNF secretion and shed light on the mechanisms that regulate this process.
Original research paper Nature Reviews Neuroscience 10 10 168 - 169 doi:10.1038/nrn2597