Regulation of mitochondrial morphology and cell survival by Mitogenin I and mitochondrial single-stranded DNA binding protein

Arakaki, Naokatu; Nishihama, Takeshi; Kohda, Akira; Owaki, Hiroyuki; Kuramoto, Yoshinori; Abe, Reika; Kita, Takafumi; Suenaga, Masaya; Himeda, Toshiki; Kuwajima, Masamichi; Shibata, Hirofumi; Higuti, Tomihiko

doi:10.1016/j.bbagen.2006.05.012

Cited by 35 publications

(35 citation statements)

References 26 publications

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“…Because only a distinct fraction of the cells showed pronounced nuclear staining, the possibility was raised that the subcellular distribution might depend on the cell cycle status. This agrees with data mentioned by Arakaki et al, who found PDIP38 (here called mitogenin I) to be located in the nucleus during the G 2 /M to the late G 1 phase (36). Indeed, we could show that no PDIP38 localized to the nuclei in confluent, non-proliferating NBT-II cells, but that clustering of CEACAM1 induced nuclear translocation of PDIP38 in the majority of the quiescent NBT-II cells.…”

Section: Discussionsupporting

confidence: 82%

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

Klaile

Kannicht³

et al. 2007

Journal of Biological Chemistry

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The homophilic cell-cell adhesion receptor CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1, CD66a) acts as a regulator of contact-dependent cell survival, differentiation, and growth. It is involved in the control of proliferation in hematopoietic and epithelial cells and can act as a tumor suppressor. In this study, we identify DNA polymerase ␦-interacting protein 38 (PDIP38) as a novel binding partner for CEACAM1-L and CEACAM1-S. We show that PDIP38 can occur in the nucleus, in the cytoplasm and at the plasma membrane in NBT-II, IEC18, RBE, and HeLa cells and that the distribution in NBT-II cells is influenced by the confluency of the cells. We also demonstrate that the interaction of CEACAM1 and PDIP38 is of functional importance in NBT-II cells, which co-express the long and the short CEACAM1 isoform. In subconfluent, proliferating NBT-II cells, perturbation of CEACAM1 by antibody clustering induces increased binding to PDIP38 and results in rapid recruitment of PDIP38 to the plasma membrane. The same treatment of confluent, quiescent NBT-II cells leads to a different response, i.e. translocation of PDIP38 to the nucleus. Together, our data show that PDIP38 can shuttle between the cytoplasmic and the nuclear compartments and that its subcellular localization is regulated by CEACAM1, implicating that PDIP38 may constitute a novel downstream target of CEACAM1 signaling.The fate of a cell is controlled by its environment, including the extracellular matrix, neighboring cells, and soluble factors. The signals mediated by this environment frequently are transduced by components of cell-matrix or cell-cell adhesion complexes, like integrins, Ig-cell adhesion molecules, or cadherins (1). CEACAM1 3 (carcinoembryonic antigen-related cell adhesion molecule 1) is a cell-cell adhesion receptor belonging to the CEA family within the Ig-like cell adhesion molecules. CEACAM1 acts as an important regulator of contactdependent control of cell survival, differentiation, and growth in various normal and transformed/cancerous cells of epithelial, endothelial, and hematopoietic origin, as reviewed previously (2, 3).The two major CEACAM1 isoforms are co-expressed in most cells and consist of four extracellular Ig-like domains, a transmembrane domain, and, as a result of differential splicing, a long (L, 71 aa) or a short (S, 10 aa) cytoplasmic domain. Both isoforms mediate cell-cell adhesion via homophilic binding (4, 5). CEACAM1 can also bind to other CEA family members (6) and is used as a receptor by viral and bacterial pathogens (7-9). Recent studies show that there is an important role for CEACAM1 in modulating the immune responses associated with infection, inflammation, and cancer, as reviewed previously (10, 11). CEACAM1 controls differentiation processes (12-14) and apoptosis (13,(15)(16)(17) and can act as a tumor suppressor, as reviewed before (2, 18). We have previously demonstrated that CEACAM1 is implicated in the regulation of proliferation and contact inhibition in epithelial NBT-II cells (19, *...

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Section: Discussionsupporting

confidence: 82%

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

Klaile

Kannicht³

et al. 2007

Journal of Biological Chemistry

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“…Immunofluorescence studies of endogenous PDIP38 as well as of ectopically expressed C-terminally-tagged EGFP constructs showed that they are localized to the mitochondria [154]. Similar fractionation and immunofluorescence studies in two other studies confirmed these findings with the further indication that PDIP38 is present in the mitochondria matrix [186,187]. PDIP38 was found to associate with mt SSB (mitochondrial single stranded binding protein) and with the mitochondrial DNA nucleoid/mitochromosome [186,187].…”

Section: Pdip38 Is a Mitochondrial Protein With Multiple Subcellular supporting

confidence: 72%

“…PDIP38 was found to associate with mt SSB (mitochondrial single stranded binding protein) and with the mitochondrial DNA nucleoid/mitochromosome [186,187]. The functions of PDIP38 in mitochondria are still unclear; in addition to potential effects on mitochondrial DNA replication, its depletion affects mitochondrial morphology [187], raising a question of whether the effects of its depletion also impacts mitochondrial energy metabolism.…”

Section: Pdip38 Is a Mitochondrial Protein With Multiple Subcellular mentioning

confidence: 99%

Regulation and Modulation of Human DNA Polymerase δ Activity and Function

Lee

Wang

Zhang

et al. 2017

Preprint

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This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

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“…However, our efforts to detect any interaction between these proteins or any effect of PDIP38 on polymerase ␥ activity have been unsuccessful (data not shown). The precise role of this protein in mitochondria is still unknown, although a recent publication reported that its down-regulation resulted in mitochondrial fragmentation (29).…”

Section: Journal Of Biological Chemistry 3667mentioning

confidence: 99%

The Layered Structure of Human Mitochondrial DNA Nucleoids

Bogenhagen

Rousseau

Burke

2008

Journal of Biological Chemistry

382

353

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Mitochondrial DNA (mtDNA) occurs in cells in nucleoids containing several copies of the genome. Previous studies have identified proteins associated with these large DNA structures when they are biochemically purified by sedimentation and immunoaffinity chromatography. In this study, formaldehyde cross-linking was performed to determine which nucleoid proteins are in close contact with the mtDNA. A set of core nucleoid proteins is found in both native and cross-linked nucleoids, including 13 proteins with known roles in mtDNA transactions. Several other metabolic proteins and chaperones identified in native nucleoids, including ATAD3, were not observed to crosslink to mtDNA. Additional immunofluorescence and protease susceptibility studies showed that an N-terminal domain of ATAD3 previously proposed to bind to the mtDNA D-loop is directed away from the mitochondrial matrix, so it is unlikely to interact with mtDNA in vivo. These results are discussed in relation to a model for a layered structure of mtDNA nucleoids in which replication and transcription occur in the central core, whereas translation and complex assembly may occur in the peripheral region.Eukaryotic cells typically contain thousands of mtDNA 2 genomes assembled into hundreds of aggregates known as nucleoids (1-3). These nucleoids show considerable dynamic stability, raising the possibility that this higher order organization is very important to the inheritance and segregation of mtDNAs. Nucleoid organization is thought to contribute to the rapid segregation of mtDNA mutations during oocyte maturation, the so-called "bottleneck" (4, 5), since early primordial germ cells appear to have only a small number of segregation units (6). The degree of mtDNA heteroplasmy varies considerably during embryonic development of somatic tissues as well, reflecting an uneven distribution of mtDNA genotypes that may be influenced by the clustered organization of mtDNA. A high rate of mitochondrial fusion appears to be essential for the maintenance of mtDNA in nucleoids (7,8). One of the consequences of active cycling of mitochondrial fusion and fission may be to permit an individual nucleoid to have access to a larger pool of diffusible proteins required for replication or transcription than it would if it were trapped within a single mitochondrion.Quantitative analysis of the size and mtDNA content of nucleoids in cultured mammalian cells suggests that an average nucleoid may contain 5-7 mtDNA genomes packed in a space with a diameter of only 70 nm (9). A human mtDNA nucleoid with seven 16.6-kb mtDNA genomes is a large structure containing 70 million daltons of DNA and a comparable mass of protein. These nucleoids resemble their counterparts in eubacteria, which employ abundant basic DNA binding proteins to package their genomes in a restricted volume. The packing density of bacterial nucleoids is impressive, since 4700 kb of E. coli DNA is folded into a volume of 0.08 -0.24 m 3 (10). If 5-7 mtDNA molecules are packed in a sphere with a diameter of 70 nm, the ca...

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Regulation of mitochondrial morphology and cell survival by Mitogenin I and mitochondrial single-stranded DNA binding protein

Cited by 35 publications

References 26 publications

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

Regulation and Modulation of Human DNA Polymerase δ Activity and Function

The Layered Structure of Human Mitochondrial DNA Nucleoids

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Regulation of mitochondrial morphology and cell survival by Mitogenin I and mitochondrial single-stranded DNA binding protein

Cited by 35 publications

References 26 publications

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

Regulation and Modulation of Human DNA Polymerase &delta; Activity and Function

The Layered Structure of Human Mitochondrial DNA Nucleoids

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Product

Resources

About

Regulation and Modulation of Human DNA Polymerase δ Activity and Function