Confirmation and functional analysis of new interacting proteins that interacts with the intracellular region of the Hodgkin lymphoma marker CD30

Author(s)

Bruno Aquino

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2016-03-21

Examining board members

Jörg Kobarg; Giselle Zenker Justo; Patricia da Silva Melo; Marcio Chaim Bajgelman; Cleslei Fernando Zanelli

• Advisor: Jörg Kobarg

Abstract

CD30 is a membrane-associated glycoprotein classified as type I tumor necrosis factor receptor. This protein is overexpressed in Hodgkin and Reed-Sternberg cells characteristic of Hodgkin lymphoma. When CD30 is stimulated by binding of its ligand CD30L, pleiotropic effects result, including proliferation, activation, differentiation or cell death occur, depending on cell¿s type and maturation stage. NF?B signalling pathway is activated by CD30 when it interacts with the adapter protein TRAF5, causing stimulation of cell proliferation. Some other proteins (TRAF 1, 2 and 3; ARNT) also interact with the intracellular portion of CD30. Hence, the aim of this study was to identify new proteins that interact with the cytosolic tail of CD30 in order to understand the effects of CD30 on the cellular metabolism. Results of this study confirmed the interaction of CD30 with TRAF5 and detected new interactor proteins like creatine kinase (CK), vimentin and phosphoglycerate mutase (PGAM1). The interaction between CD30 and CK occurs in a protein conserved region, the D1 subdomain. Colocalization experiments indicated that the intracellular portion has a cytosolic distribution, instead of locating in the membrane, as expected for CD30. Moreover, when CD30 was expressed in MDA-MB-231 there was an increase in the membrane potential and viability dependent on the D1 subdomain. These results suggest an important role of the interaction between CD30 and CK in energy metabolism and may be an important target for the treatment of Hodgkin lymphoma (AU)

• FAPESP's process: 11/20086-1 - Confirmation and functional analysis of the interaction of new proteins that interact with the cytoplasmic region of CD30 the marker protein for Hodgin lymphoma
• Grantee: Bruno Aquino
• Support Opportunities: Scholarships in Brazil - Doctorate