Oncogenic MAPK signaling in regulating anti-tumor immunity
Abstract:
Mitogen-activated protein kinases (MAPKs) are fundamental enzymes controlling basic cellular functions. While most of the MAPKs are studied in the context of tumorigenesis, the role of MAPK in immune regulation is not well understood. Here, we will investigate the role of both typical and atypical MAPKs in regulating anti-tumor immunity. We will decipher the role of MAPKs in controlling the tumor secretome and further characterize their intrinsic role in controlling DC maturation and activation. These studies will enable us to adroitly administer kinase inhibitors in synergistic therapeutic regimes to augment anti-tumor immunity.
Principal investigator:
Univ.-Prof. Dr. rer. nat. Krishnaraj Rajalingam
Molecular Signaling Unit (MSU) am Institut für Immunologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-8051
E-mail: krishna@uni-mainz.de
Web: https://www.msu-mainz.com
PostDoc:
Dr. Sebastian Rosigkeit
Project-related publications:
Mooz J, Oberoi-Khanuja TK, Harms GS, Wang W, Jaiswal BS, Seshagiri S, Tikkanen R, Rajalingam K. (2014) Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration. Sci Signal.7(337):ra73.
Takeda AN, Oberoi-Khanuja TK, Glatz G, Schulenburg K, Scholz RP, Carpy A, Macek B, Remenyi A, Rajalingam K (2014) Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and CIAP1. EMBOJ 33(16):1784-801.
Oberoi TK, Dogan T, Hocking JC, Scholz RP, Mooz J, Anderson CL, Karreman C, Meyer zu Heringdorf D, Schmidt G, Ruonala M, Namikawa K, Harms GS, Carpy A, Macek B, Köster RW, Rajalingam K (2012) IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation. EMBO J. 4;31(1):14-28.
Dogan T, Harms GS, Hekman M, Karreman C, Oberoi TK, Alnemri ES, Rapp UR, Rajalingam K (2008) X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. Nat Cell Biol. 10(12):1447-55
Rajalingam K, Wunder C, Brinkmann V, Churin Y, Hekman M, Sievers C, Rapp UR, Rudel T. (2005) Prohibitin is required for Ras induced Raf-MEK-ERK activation and epithelial cell migration. Nat Cell Biol. 7(8):837-43.