NOA36/ZNF330 is a conserved cystein-rich protein with proapoptotic activity in human cells.
Translocations of regulator proteins from or to the mitochondria are key events in apoptosis regulation. NOA36/ZNF330 is a highly evolutionary conserved protein with a characteristic cystein-rich domain. In this work we address its mitochondrial localization and we demonstrate that a blockage of endogenous NOA36/ZNF330 expression by small-interfering RNA (siRNA) reduced apoptotic response to etoposide (ETO), camptothecin (CPT) and staurosporine (STS) but not to CH11 anti-Fas antibody or tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) in HeLa cells. In contrast, when ectopically expressed in the cytoplasm, NOA36/ZNF330 induces apoptotic cell death. We also found that the domain responsible for this proapoptotic activity is located its cystein-rich region. We propose that NOA36/ZNF330 is translocated from the mitochondria to the cytoplasm when apoptosis is induced and that it contributes to cytochrome c release.
de Melo
Ivan S
IS
Departamento de Biomedicina, Biotecnología y Salud Pública, Universidad de Cádiz, 1150 Puerto Real, Spain.
Iglesias
Concepción
C
Benítez-Rondán
Alicia
A
Medina
Francisco
F
Martínez-Barberá
Juan Pedro
JP
Bolívar
Jorge
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D045304:Cytochromes c / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C435644:ZNF330 protein, human; D045304:Cytochromes c