An Inhibitor of the F1 Subunit of ATP Synthase (IF1) Modulates the Activity of Angiostatin on the Endothelial Cell Surface

R., Burwick, Nick; Wahl, Michael J.; Fang, Jun; Zhong, Zhaoxi; Moser, Tammy L.; Li, Bo; Capaldi, Roderick A.; Kenan, Daniel J.; Pizzo, Salvatore V.

doi:10.1074/jbc.m405947200

Cited by 72 publications

(61 citation statements)

References 46 publications

(39 reference statements)

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“…Because IF1 dissociates from F 1 F O ATP synthase below pH 6.5, one would expect it to be dissociated, and possibly removed, from the EC surface in the tumor microenvironment. As discussed below, we recently reported that angiostatin and IF1 can compete with each other for ATP synthase binding [Burwick et al, 2005]. These findings suggest but do not prove that angiostatin binds to ATP synthase in proximity to the IF1 binding pocket.…”

Section: Atp Synthase: a Cell Surfacementioning

confidence: 85%

“…2). Studies using isolated mitochondria and intact EC showed that although IF1 blocked ATP hydrolysis in both cases, which caused conservation of ATP on the cell surface, it did not block ATP synthesis [Burwick et al, 2005]. In contrast, angiostatin blocked both ATP synthesis and hydrolysis.…”

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 93%

“…In the most recent collaboration between these two investigators, recombinant angiostatin (from Sigma Chem. Co., St. Louis, MO), native angiostatin from Collaborative (Calbiochem, San Diego, CA), and native angiostatin prepared in-house all gave identical activities when comparing extracellular pH 7.3-6.7 [Burwick et al, 2005].…”

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 99%

“…In vitro tube differentiation assays showed that IF1 did not inhibit tube formation, but angiostatin did. The relative concentrations of angiostatin and IF1 may modulate new blood vessel development during angiogenesis [Burwick et al, 2005]. It is noteworthy that IF1 effects are strongly modulated by pH, similar to angiostatin, which should confer specificity for the tumor microenvironment.…”

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 99%

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Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

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114

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Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as ''angiogenesis'' [Folkman (1971) N Engl J Med 285:1182-1186. These new vessels arise from local capillaries, arteries, and veins in response to the release of soluble growth factors from the tumor mass, enabling these tumors to grow beyond the diffusion-limited size of approximately 2 mm diameter. Angiostatin, a naturally occurring inhibitor of angiogenesis, was discovered based on its ability to block tumor growth in vivo by inhibiting the formation of new tumor blood vessels [O'Reilly et al. (1994a) Cold Spring Harb Symp Quant Biol 59:471-482]. Angiostatin is a proteolytically derived internal fragment of plasminogen and may contain various members of the five plasminogen ''kringle'' domains, depending on the exact sites of proteolysis. Different forms of angiostatin have measurably different activities, suggesting that much remains to be elucidated about angiostatin biology. A number of groups have sought to identify the native cell surface binding site(s) for angiostatin, resulting in at least five different binding sites proposed for angiostatin on the surface of endothelial cells (EC). This review will consider the data supporting all of the various reported angiostatin binding sites and will focus particular attention on the angiostatin binding protein identified by our group: F 1 F O ATP synthase. There have been several developments in the quest to elucidate the mechanism of action of angiostatin and the regulation of its receptor. The purpose of this review is to describe the highlights of research on the mechanism of action of angiostatin, its' interaction with ATP synthase on the EC surface, modulators of its activity, and issues that should be explored in future research related to angiostatin and other anti-angiogenic agents.

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Section: Atp Synthase: a Cell Surfacementioning

confidence: 85%

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 93%

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 99%

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 99%

See 2 more Smart Citations

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

Self Cite

114

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“…His-tagged ATP synthase subunit a was expressed in E. coli, 35 and His-tagged-IF 1 . 36 The His-tagged ATP synthase subunit a and the IF 1 were batch purified using Qiagen Ni-NTA-agarose under native conditions according to the manufacturer's instructions.…”

Section: Atp Generation By Bioluminescent Luciferase Assaymentioning

confidence: 99%

Amyloid precursor protein and amyloid β-peptide bind to ATP synthase and regulate its activity at the surface of neural cells

et al. 2007

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Amyloid precursor protein (APP) and amyloid b-peptide (Ab) have been implicated in a variety of physiological and pathological processes underlying nervous system functions. APP shares many features with adhesion molecules in that it is involved in neurite outgrowth, neuronal survival and synaptic plasticity. It is, thus, of interest to identify binding partners of APP that influence its functions. Using biochemical cross-linking techniques we have identified ATP synthase subunit a as a binding partner of the extracellular domain of APP and Ab. APP and ATP synthase colocalize at the cell surface of cultured hippocampal neurons and astrocytes. ATP synthase subunit a reaches the cell surface via the secretory pathway and is N-glycosylated during this process. Transfection of APP-deficient neuroblastoma cells with APP results in increased surface localization of ATP synthase subunit a. The extracellular domain of APP and Ab partially inhibit the extracellular generation of ATP by the ATP synthase complex. Interestingly, the binding sequence of APP and Ab is similar in structure to the ATP synthase-binding sequence of the inhibitor of F1 (IF 1 ), a naturally occurring inhibitor of the ATP synthase complex in mitochondria. In hippocampal slices, Ab and IF 1 similarly impair both short-and long-term potentiation via a mechanism that could be suppressed by blockade of GABAergic transmission. These observations indicate that APP and Ab regulate extracellular ATP levels in the brain, thus suggesting a novel mechanism in Ab-mediated Alzheimer's disease pathology.

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Proteomic Techniques and Their Applications

Juan

2019

Biomolecular and Bioanalytical Techniques

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An Inhibitor of the F1 Subunit of ATP Synthase (IF1) Modulates the Activity of Angiostatin on the Endothelial Cell Surface

Cited by 72 publications

References 46 publications

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Amyloid precursor protein and amyloid β-peptide bind to ATP synthase and regulate its activity at the surface of neural cells

Proteomic Techniques and Their Applications

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