Large Tumor Suppressor 1 (Lats1) Regulation in Growth Control

During the course of development, cells undergo numerous rounds of cell division followed by differentiation to form a unique functional unit called an organ. Once an organ reaches to a certain size, its size is maintained throughout the organism’s lifetime. This whole process is accomplished by factors that signal between and within cells.

Hippo pathway is a signaling pathway that suppresses cell division and promotes cell death. One of the main components in the pathway is a kinase called Large Tumor Suppressor 1 (Lats1). Lats1 blocks the oncogenic activity of its downstream substrate, Yes-Associated Protein 1 (Yap1), through phosphorylation. Lats1 is ubiquitously expressed in our body but, interestingly, some organs and transformed cells express a shorter isoform of Lats1 (sLats1) which lacks its kinase domain. It has been speculated that the regions outside of the kinase domain of Lats1 serves as a regulatory site, such as sites for protein-protein interaction, subcellular localization or other post-translational modifications. However, the role of sLats1 remains unknown.

Here, I demonstrate sLats1 plays an opposite role from Lats1 and may function as an activator of Yap1, using a human cell line. Overexpression of sLats1 results in de-phosphorylation and nuclear localization of Yap1. Activation of Yap1 by sLats1 was also observed through increased expression of genes regulated by Yap1. I will further investigate how sLats1 accomplishes this without its kinase domain. To address this question, I will test several aspects, such as reduction of the kinase activity of Lats1 and other kinases, enhancement of any phosphatase activity, and inhibition of Yap1 from phosphorylation.

Files

Metadata

Work Title Large Tumor Suppressor 1 (Lats1) Regulation in Growth Control
Access
Penn State
Creators
  1. Matsui, Yurika
Keyword
  1. Growth control
  2. Hippo pathway
  3. Large Tumor Suppressor 1 (Lats1)
License Attribution-NonCommercial-NoDerivs 3.0 United States
Work Type Poster
Deposited February 29, 2016

Versions

Analytics

Collections

This resource is currently not in any collection.

Work History

Version 1
published

  • Created
  • Added 12j62s477t_version1_yum111_ECoS.pdf
  • Added Creator Matsui, Yurika
  • Published