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RasGAPs: Hyperactive Ras in Developmental Disorders and Cancer

RasGAPs play a crucial role in regulating Ras signaling pathways, affecting cell proliferation, differentiation, and survival. Mutations in Ras and its regulators are linked to various syndromes and cancers, influencing tumor progression and response to therapy.

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RasGAPs: Hyperactive Ras in Developmental Disorders and Cancer

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  1. 14 RasGAPs

  2. Hyperactive Ras in developmentaldisorders and cancerSuzanne Schubbert*, Kevin Shannon*‡ and Gideon Bollag

  3. Ras Receptorswitchefetor Proliferação, diferenciação, sobrevivência Mutação em muitos tumores = oncogenic ras Envolvido em outras anomalias Mutação NF1 (regulador negativo)neurofibromatose Mutação PTP11 (fosfatase com SH2)desenv. (face, coração) Mutação em KHAS, RHAS, ERK, MEKvárias síndromes GNEFs (SOS) = desligam GDPGTP abunda EFETORES (Raf) = mais de 20, recebem sinal GAPs = afetam duração do sinal (GTPase) EGFproliferação; NGFdiferenciação de PC12 TransitórioDuradouro

  4. Survivin Variantes de splicing múltiplos (só 3 caracterizados) Vários compartimentos e muita modificação pós-traducional cinetócoro, centrosomo e fuso; citosol, mitocondria e núcleo Controle de ciclo celular (p53 reprime BIRC5) Reguladora de morte apoptótica ou não apoptótica Se soltar do fuso  caspase 3 Resposta a estresse de tumores Sobrevivência em meio desfavorável (mitose tumoral) Homeostase tecidual preservando vida de tecidos Em tumores: Marcador tumor específico, dos melhores Angiogênese tumoral Resistência a drogas anticancer!

  5. Homodimérica polymerized microtubules and electrostatic interactions with chromosomal passenger proteins, (carboxy terminus α helices, inner centromere protein antigens (INCENP), Lys112 and Lys120; borealin, Lys110, Lys121 and Arg132) XPO1 /nuclear export sequence (NES, Val89–Leu98) SMAC (Leu64, Leu87) X-linked IAP (XIAP) (Lys15–Met38) heat shock protein 90 (HSP90, Lys79–Lys90) mitochondrial-targeting sequence (survivin-ΔEx-3 C terminus) borealin and INCENP (dimer interface hydrophobic pocket: Leu6, Trp10, Phe93, Phe101 and Leu102)

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