title: Dynamics of RASSF1A/MOAP-1 association with death receptors.
abstract: RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis utilizing the Bax-interacting protein MOAP-1 (previously referred to as MAP-1). However, the dynamics of death receptor recruitment of RASSF1A and MOAP-1 are still not understood. We have now detailed recruitment to death receptors (tumor necrosis factor receptor 1 [TNF-R1] and TRAIL-R1/DR4) and identified domains of RASSF1A and MOAP-1 that are required for death receptor interaction. Upon TNF-alpha stimulation, the C-terminal region of MOAP-1 associated with the death domain of TNF-R1; subsequently, RASSF1A was recruited to MOAP-1/TNF-R1 complexes. Prior to recruitment to TNF-R1/MOAP-1 complexes, RASSF1A homodimerization was lost. RASSF1A associated with the TNF-R1/MOAP-1 or TRAIL-R1/MOAP-1 complex via its N-terminal cysteine-rich (C1) domain containing a potential zinc finger binding motif. Importantly, TNF-R1 association domains on both MOAP-1 and RASSF1A were essential for death receptor-dependent apoptosis. The association of RASSF1A and MOAP-1 with death receptors involves an ordered recruitment to receptor complexes to promote cell death and inhibit tumor formation.
authors.affiliation: Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Foley
authors.forename: Holly
authors.initials: H
authors.lastname: Freedman
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Choo
authors.forename: Christina
authors.initials: C
authors.lastname: Onyskiw
authors.forename: Nai Yang
authors.initials: NY
authors.lastname: Fu
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yu
authors.forename: Jack
authors.initials: J
authors.lastname: Tuszynski
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Pratt
authors.forename: Shairaz
authors.initials: S
authors.lastname: Baksh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D053218:Receptors, Death Domain / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C428449:MOAP1 protein, human; C411762:RASSF1 protein, human; D053218:Receptors, Death Domain; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D047888:Receptors, Tumor Necrosis Factor, Type I; D025521:Tumor Suppressor Proteins