creator Zhao, Yu advisor Xiang, Jialing Ubiquitin-like protein 4A (Ubl4A) was identified as a housekeeping gene at X chromosome. It involves in the guided entry of tail-anchored (GET) protein pathway in which tail-anchored (TA) proteins are transported to endoplasmic reticulum (ER). However, Ubl4A also involves other functions not related to GET pathway, such as tumor suppression and DNA damage-mediated apoptosis. Up to date, the function of Ubl4A in mammals is still largely unknown. We found that either overexpression or knockdown of Ubl4A promoted cell death in cell culture system. Using an in vivo genetic knockout system, we found that Ubl4A knockout mice displayed a high neonatal mortality and had a defect in glycogen synthesis, which is mainly controlled by a key protein kinase Akt. Loss of Ubl4A resulted in the impairment of insulin-induced Akt translocation to the plasma membrane, an essential step for Akt activation. We demonstrated that Ubl4A directly interacted with actin-related protein 2/3 (Arp2/3) complex, further accelerated Arp2/3 complex-dependent actin branching, thereby bringing Akt to proximity into the plasma membrane for activation. Furthermore, we showed that Ubl4A-mediated actin branching also played important roles in other cellular activities, such as formations oflamellipodia and filopodia, macrophage phagocytosis, wound healing, and neutrophil chemotaxis. These findings provide us a new insight into understanding the roles of Ubl4A in cellular function and a molecular basis for treatment of related human diseases. Submitted by Erma Thomas (thomase@iit.edu) on 2016-03-29T18:29:00Z No. of bitstreams: 1 etdadmin_upload_390163.zip: 2870238 bytes, checksum: 361cc56a5254167d5318a83a3cbae652 (MD5) Made available in DSpace on 2016-03-29T18:29:00Z (GMT). No. of bitstreams: 1 etdadmin_upload_390163.zip: 2870238 bytes, checksum: 361cc56a5254167d5318a83a3cbae652 (MD5) Previous issue date: 2015-12 Ph.D. in Biology, December 2015 2015 2015-12 http://hdl.handle.net/10560/3762 en Akt Arp2/3 Cell migration Insulin Ubl4A Dissertation born digital application/pdf In Copyright http://rightsstatements.org/page/InC/1.0/ Restricted Access BIOL / Biology Illinois Institute of Technology Affiliated department