Dynamics of RASSF1A/MOAP-1 association with death receptors.
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.
Foley
Caitlin J
CJ
Division of Experimental Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
Freedman
Holly
H
Choo
Sheryl L
SL
Onyskiw
Christina
C
Fu
Nai Yang
NY
Yu
Victor C
VC
Tuszynski
Jack
J
Pratt
Joanne C
JC
Baksh
Shairaz
S
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*
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