| Citation | Marc Kirschner has made outstanding contributions to two major areas of cell bilolgy; the dynamics of microtubule growth and cell cycle regulated proteolysis. Microtubules are responsible not only for the segregation of chromosomes to opposite poles of the cell during mitosis but also for the transport of organelles and macromolecules to different parts of the cell. Marc Kirschner's work has addressed how cells ensure that microtubules form at the right place and time. His work has identified two vital properties of microtubules; their ability to be nucleated by spedcific strictures, such as centrosomes and kinetochores and their 'dynamic instability'. which enables microtubules to 'search' cellular space. Kirschner not only pioneered the observation of microtubule dynamics but also suggested a powerful 'molecular' explanation for them, according to which hydrolysis of GTP bound to each tubulin subunit increases the probability of their dissociation from the ends of microtubules. This means that microtubules grow as long as the subunits in their caps contain GTP but shrink if they contain GDP. This concept explains how at any one point in time some of the cell's microtubules are growing while others are shrinking. It has contributed greatly to our understanding of the eukaryotic cell's cytoskeleton. Marc Kirschner's second major contribution has been in understanding cell cycle regulatory mechanisms, in particular the role of proteolysis mediated by ubiquitination. Cyclins are unstable regulatory subunits of cyclin dependent kinases (known as CDK's). Marc Kirschner's lab identified within the N-termini of cyclins a specific sequence known as their destruction box, which is essential for cyclin degradation at the metaphase to anaphase transition. They further showed that non-degradeable cyclins lacking their destruction boxes prevent inactivation of the mitotic CDK and cause cells to arrest in mitosis. His lab showed that cyclin destruction boxes were essential for cyclin ubiquitination, which precedes and is essential for proteolysis by the proteosome. They identified a large multi-subunit ubiquitin protein ligase, which is essential for cyclin ubiquitination, which is known either as the cyclosoem or the anaphase romoting complex. The APC is incolved in coordinating the degradation of many different proteins besides cyclins as cells proceed through anaphase, and its discovery by Marc Kirschner (and others) ranks along with that of cyclins and CDK's. Marc Kirschner also made several important discoveries in the area of amphibian development biology.
Finally, Marc Kirschner is an invalubale ambassador for Cell Biology and for Science in general. He has been president of the American society of Cell biology and has been at the forefront of pioneering and successful efforts to persuade the American Congress to increase funding for biomedical science. |