title: Intermolecular association between caspase-mediated cleavage fragments of phospholipase D1 protects against apoptosis.
abstract: Phospholipase D plays an anti-apoptotic role but little is known about dynamics of phospholipase D turnover during apoptosis. We have recently identified phospholipase D1 as a new substrate of caspases which generates the N-terminal and C-terminal fragment of phospholipase D1. In the present study, we tried to investigate whether association of the caspase cleavage fragments may be involved in regulation of apoptosis. Ectopically expressed C-terminal fragment, but not N-terminal fragment of phospholipase D1, is exclusively imported into the nucleus via a nuclear localization sequence; however, endogenous C-terminal fragment of phospholipase D1 from etoposide-induced apoptotic cells and Alzheimer's disease brain tissues with active caspase-3, was localized in the cytosolic fraction as well as the nuclear fraction. Intermolecular association between the two fragments of phospholipase D1 through hydrophobic residues within the catalytic motif inhibited nuclear localization of C-terminal fragment of phospholipase D1, and two catalytic motif and nuclear localization sequence regulated nuclocytoplasmic shuttling of phospholipase D1. Moreover, hydrophobic residues involved in the intermolecular association are also required for both its enzymatic activity and anti-apoptotic function. Taken together, we demonstrate that interdomain association and dissociation of phospholipase D1 might provide new insights into modulation of apoptosis.
authors: Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, 609-735, Republic of Korea.
authors: Young Hoon
authors: YH
authors: Jang
authors: Do Sik
authors: do S
authors: Min
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000201:enzymology; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D010739:Phospholipase D / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005047:Etoposide; D010739:Phospholipase D; C106801:phospholipase D1; D020169:Caspases