title: SG2NA recruits DJ-1 and Akt into the mitochondria and membrane to protect cells from oxidative damage.
abstract: SG2NA is a WD-40 repeat protein with multiple protein-protein interaction domains of unknown functions. We demonstrate that it associates with the antioxidant protein DJ-1 and the survival kinase Akt. The C-terminal WD-40 repeat domain of SG2NA is required for its interaction with Akt, while DJ-1 binds it further upstream. No interaction between DJ-1 and Akt occurs in the absence of SG2NA. SG2NA, DJ-1, and Akt colocalize in mitochondria and plasma membrane. Their association is enhanced by increasing levels of reactive oxygen species up to a threshold level but falters thereafter with further increase in oxidants. Mutants of DJ-1 found in patients with familial parkinsonism are not recruited by SG2NA, suggesting its role in neuroprotection. Cells depleted of SG2NA are susceptible, while those overexpressing it are resistant to apoptosis induced by oxidative stress. Our study thus unravels a novel pathway of recruitment of Akt and DJ-1 that provides protection against oxidative stress, especially in neurons.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Goutam Kumar
authors.initials: GK
authors.lastname: Tanti
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: skgoswami@mail.jnu.ac.in.
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Goswami
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010300:Parkinson Disease; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D054730:Protein Interaction Domains and Motifs; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D001324:Autoantigens; D002148:Calmodulin-Binding Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; C485775:Strn3 protein, mouse; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D051057:Proto-Oncogene Proteins c-akt; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
keywords: Akt; DJ-1; Membrane; Mitochondria; Oxidative stress; Parkinson׳s disease; Striatin