Dear All

I would like to warmly invite you to our next Nencki Institute Seminar on the 12^th of October at 3pm as usual. We will host dr. Izabela Sumara, head of the Cell cycle and ubiquitin signaling laboratory at the Institut de génétique et de biologie moléculaire et cellulaire (IGBMC) in Strasbourg, France. Dr. Sumara’s lecture will be entitled: Spatial control of cell cycle progression in health and disease

Abstract

Cell cycle is a fundamental biological process that ensures organism development and its dysregulation is linked to many devastating human diseases. Correct execution of cell cycle requires cellular growth, duplication of all genetic material during S-phase followed by its precise partitioning between two daughter cells during mitosis. Through this process, not only the genetic material but also cellular organelles have to be equally distributed to newly born cells to allow for their proper functioning. Cell cycle machinery involves many proteins and enzymes that need to be precisely regulated in time and space. How is correct and timely localization of these factors to subcellular compartments regulated and how is the assembly of macromolecular complexes at correct cellular sites achieved during cell cycle transitions remain important and largely unresolved biological problems. Our team is recognized for its work on cell biology aiming to understand how localized ubiquitin signaling events drive cell cycle progression in healthy and diseased states.

In the past, our group described the role of non-proteolytic ubiquitin signaling in the regulation of mitosis establishing a concept that non-proteolytic ubiquitylation regulates localization of essential mitotic kinases. More recently our studies focused on a unique research niche aiming to dissect the cell cycle roles of ubiquitin-binding domain proteins (UBDs or ubiquitin receptors), which interact with and determine the fates of ubiquitylated substrates. I will briefly summarize our published findings in the ubiquitin field and mitosis such as on the ubiquitin receptor protein UBASH3B which drives faithful chromosome segregation and may act as an oncogenic factor. Subsequently, I will focus and discuss in detail our unpublished data on the role of the ubiquitin receptor UBAP2L as an important novel regulator of cell cycle progression. We demonstrated that UBAP2L regulates fidelity of mitotic exit through regulation of localization and stability of Polo-like kinase 1 (PLK1) as well as through biogenesis of Nuclear Pore Complexes (NPCs) during early interphase stage. Interestingly, we found that the RNA-binding proteins (RBPs) belonging to the Fragile-X related (FXR) family strongly interact with UBAP2L. Subsequent work performed in our laboratory led to the discovery of an unexpected role of FXR proteins in spatiotemporal regulation of nucleoporins (Nups) and assembly of functional NPCs during early G1, opening new avenue of research in the laboratory. Fragile X Messenger Ribonucleoprotein (FMRP) belongs to the family of FXR proteins and is missing in the neurological disorder Fragile X syndrome (FXS) for which no therapy exists to date. Our data demonstrated the same Nups and NPC defects in the models of FXS which may, in the long-term perspective, contribute to the understanding of physiopathology of FXS.

Taken together, with our research we hope to provide a better understanding of the spatial control of cell cycle progression and to identify any possible links to human pathologies.

The lecture will be followed by a get together.
With best wishes
Aleksandra Pękowska