Disease relevance of SPDYA

• An iatrogenic dissection of the left main artery with total occlusion and arrest (asystole) occurred during preoperative 4Fr coronography. "Speedy recovery" is achieved with a strategy of percutaneous primary stenting revascularization combined with cardiopulmonary maneuvers [1].

High impact information on SPDYA

• Recently, five different mammalian RINGO/Speedy family members have been reported, all of which can bind to and directly activate Cdk1 and Cdk2 [2].
• These include the RINGO/Speedy proteins, which were originally identified as regulators of the meiotic cell cycle in Xenopus oocytes [2].
• Here we report the identification and characterization of a novel cell cycle gene, designated Speedy (Spy1) [3].
• We demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2 activation [3].
• Spy1 mRNA is expressed in several human tissues and immortalized cell lines and is only expressed during the G1/S phase of the cell cycle [3].

Biological context of SPDYA

• In addition to their activation via binding to cyclins, cyclin-dependent kinases (CDKs) can be activated via binding to a novel cell cycle regulator termed Speedy/Ringo, which shows no apparent similarity to cyclins [4].
• These mammalian Speedy/Ringo proteins exhibit distinct tissue expression patterns, though all three are enriched in testis, consistent with the initial observation that Xenopus Speedy/Ringo functions during meiosis [4].
• Human Spy1 promotes survival of mammalian cells following DNA damage [5].
• Here we demonstrate that overexpression of human Spy1 enhances mammalian cell viability during cellular responses to DNA damage induced by genotoxic agents such as camptothecin, cisplatin, and hydroxyurea [5].
• Here we report a role for Spy1 in apoptosis and checkpoint activation in response to UV irradiation [6].

Anatomical context of SPDYA

• Speedy/Ringo A is widely expressed in tissues and cell lines [4].
• Similar to its Xenopus counterpart, human Speedy is able to induce oocyte maturation, suggesting similar biological characteristics [3].

Associations of SPDYA with chemical compounds

• In 191 (86%) procedures a fixed-wire system was used (ACE Scimed, Probe USCI, Orion Cordis), and in 30 (14%) a monorail system (Speedy Schneider, Express Scimed) [7].

Regulatory relationships of SPDYA

• We demonstrate that Spy1 expression inhibits phosphorylation of Chk1, RPA, and histone H2A.X, which may directly contribute to the decrease in apoptosis and checkpoint bypass [6].

Other interactions of SPDYA

• Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2 [3].
• Hence, human Speedy is a novel cell cycle protein capable of promoting cell proliferation through the premature activation of cdk2 at the G1/S phase transition [3].
• Spy1 is the originally identified member of the Speedy/Ringo family of vertebrate cell cycle regulators, which can control cell proliferation and survival through the atypical activation of cyclin-dependent kinases [6].
• Spy1 Expression Prevents Normal Cellular Responses to DNA Damage: INHIBITION OF APOPTOSIS AND CHECKPOINT ACTIVATION [6].
• Speedy (Spy1), a novel cell cycle regulatory protein, has been found to prematurely activate CDK2 when microinjected into Xenopus oocytes and when expressed in mammalian cells [8].

Analytical, diagnostic and therapeutic context of SPDYA

• Clonogenic survival assays and comet assays also show that Spy1 expression enhances cell survival after DNA damage [5].
• The diameter of the Schneider Magical Speedy balloons at secondary dilatations with 16 +/- 3 atm (14-20) was 4.1 +/- 0.4 mm (3.3-4.5) (P = 0.50 compared to the initial balloon diameter) [9].
• Patient care. Speedy access [10].

References