Vitamin D3-induced Apoptosis of Murine Squamous Cell Carcinoma Cells

McGuire, Terence F.; Trump, Donald L.; Johnson, Candace S.

doi:10.1074/jbc.m010101200

Cited by 125 publications

(37 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mitotic proteolytic cleavage site in MEK1 appears to be located after residue 51 because GFP-MEK1⌬N51 remained sensitive to mitotic cleavage. The MEK1 N-terminal region contains an ERK-binding domain, and deletion or proteolytic removal of this domain by anthrax toxin lethal factor or caspases renders MEK1 incapable of activating ERK (29,30). Here we show that, in asynchronous cell populations, the loss of the ERK-binding domain is sufficient to completely inhibit cytosolic ERK activation, but that the ERKbinding domain is not required for MEK1⌬N51 to activate membrane-bound ERK.…”

Section: Discussionmentioning

confidence: 79%

Mechanism of Mitosis-specific Activation of MEK1

Harding

Giles

Burgess

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 79%

Mechanism of Mitosis-specific Activation of MEK1

Harding

Giles

Burgess

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Floating cells have typical features of apoptotic cells, such as annexin labeling and cleavage of procaspase-9. Thus, the increase in floating cells could be considered an apoptotic index, as it occurs in response to other apoptotic stimuli (28). When we analyzed attached cells, apoptotic parameters were observed in those that overexpressed ANT1 at 4 h, almost disappearing later by 24 h.…”

Section: Discussionmentioning

confidence: 99%

Recruitment of NF-κB into Mitochondria Is Involved in Adenine Nucleotide Translocase 1 (ANT1)-induced Apoptosis

Zamora

Meroño

Viñas³

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Overexpression of adenine nucleotide translocase-1 (ANT1) is known to induce apoptosis (Bauer, M. K., Schubert, A., Rocks, O., and Grimm, S. (1999) J. Cell Biol. 147, 1493-1501), but the mechanisms involved remain unclear. In this study we show that ANT1 overexpression results in a recruitment of the IB␣-NF-B complex into mitochondria, with a coincident decrease in nuclear NF-B DNA binding activity. In this situation, NF-B transcriptionally regulated genes with antiapoptotic activity, such as Bcl-XL, MnSOD2, and c-IAP2, are down-regulated, and consequently, cells are sensitized to apoptosis. Accordingly, co-expression of p65 partially interferes with the proapoptotic effect of ANT1 overexpression. Despite the high identity of the two isoforms, overexpression of ANT2 does not exert an apoptotic effect; this lack of apoptotic activity is correlated with the absence of mitochondrial IB␣-NF-B recruitment or changes in NF-B activity. Thus, we propose that the mitochondrial recruitment of NF-B observed following ANT1 overexpression has an important role in ANT1 proapoptotic activity.Apoptosis is a form of cell death that plays a role in development, tissue homeostasis, and disease (1). The induction of apoptosis is governed by an elaborate array of checks and balances in the cell. Studies of apoptosis induction in "in vitro" systems have demonstrated that mitochondria are required for the apoptosis stimulated by a variety of different factors (2).The ANT 1 protein is localized in the inner mitochondrial membrane and exchanges cytosolic ADP for mitochondrial ATP (3). Three isoforms (ANT1, ANT2, and ANT3) with tissuespecific expression patterns have been described in humans (4). ANT interacts with several proteins of the outer mitochondrial membrane (peripheral benzodiazepine receptor, porin/VDAC, and Bax) as well as the matrix (cyclophilin D) to form the permeability transition pore (PTP) (5). The PTP appears to be an important regulator of the apoptotic process. Opening of the pore leads to a loss of mitochondrial transmembrane potential, ⌬⌿ m , which can ultimately culminate in matrix swelling and outer membrane rupture, allowing the release of apoptogenic proteins such as cytochrome c, apoptosis-inducing factor, and procaspases (6, 7). Proteins of the bcl-2 family essentially control the release of cytochrome c. Antiapoptotic members of the family (Bcl-2 and Bcl-XL) prevent cytochrome release, whereas the proapoptotic members Bax and Bak exert the opposite effect (8). Bax has been shown to interact with ANT to induce PTP opening and cytochrome c release (9). Several pharmacological compounds interfere with PTP. For instance, cyclosporin A, through its binding to cyclophilin D, prevents PTP opening, and bongkrekic acid and atractyloside are, respectively, a blocker and an inducer of apoptosis via binding of two different conformational states of ANT (10). In addition, alongside their modulation of pore formation by ANT, Bcl-2 and Bax also have been reported to influence ANT ADP/ATP antiporter activity (11). Although ...

show abstract

“…14,15 Little or no apoptosis is induced by 1,25D 3 in SCC cells when the entire population is assessed. 14,16 In the fraction of floating SCC cells following 1,25D 3 treatment, apoptosis can be detected, 17 suggesting that the floating cells account for a small part of the whole population. The ability of inecalcitol to induce apoptosis appears to be cell type-specific.…”

Section: Discussionmentioning

confidence: 99%