Lingqing Xu

  • Laboratory Instructor

Contact

Office: (412) 648-4244
117 Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

During mitosis in eukaryotes, a microtubule-based structure called the mitotic spindle needs to be correctly formed in order for duplicated chromosomes to accurately align and segregate. This requires the coordination of microtubules and many motor proteins including kinesin superfamily proteins. A typical kinesin contains a motor domain which binds to the microtubule, and a stalk and tail domain which uses energy from ATP hydrolysis to drive conformational changes that generate the motile force used for cargo transport. My project focuses on the function of two of the motor proteins, Eg5/Kinesin-5 and Kid/Kinesin-10, but in a very different context, namely their role in protein synthesis.

Processivity Model for Eg5: ribosomes are associated with microtubules through Eg5 and Eg5 is required for the elongation step of translation as well as for the processivity of the ribosome. (Model is drawn by Dr. Kristen Bartoli and modified by Lingqing Xu)

Recently, our lab identified a novel role for Eg5 during interphase in protein translation. Our hypothesis is that Eg5 acts as a link between ribosomes and microtubules to keep ribosomes from falling off the mRNA during translation. We believe that when the ATPase activity of Eg5 is chemically inhibited, the motility of Eg5 is diminished, leading to a drag on ribosomes but maintaining connection with the microtubule. Loss of Eg5 leads to an increase in 80S ribosomes, consistent with a drop-off phenotype. As Eg5 has been considered as a good target for anti-cancer drugs and several anti-Eg5 compounds are going through phase I and II trials currently, this project will suggest additional caution and investigation on targeting Eg5 in cancer treatment.

Kid is a second kinesin protein that we believe plays a role in protein synthesis. Different from Eg5 whose predominant localization is in cytoplasm, Kid was found to localize prominently to nucleoli (Kristen Bartoli, unpublished data), suggesting possible roles in protein synthesis or ribosomal biogenesis. In addition, we found that knock down of Kid resulted in an increase in protein synthesis, which is the opposite phenotype to knock down of Eg5. Our hypothesis is that Kid functions differently from Eg5 in translation and either binds to DNA and influences transcription, or binds to mRNA and blocks translation of specific proteins.

Dr. Xu earned her PhD from the University of Pittsburgh and joined the department as a faculty member in 2018.