Phosphoinositide 3-kinase

La phosphoinositide 3-kinase (PI 3-kinase, PI3K, PI(3)K, or PI-3K) est une enzyme permettant la transformation des phosphoinositides en phosphatidylinositol-3-phosphate.

Structure

Elle possède huit isoformes regroupées en trois classes[1].

Rôles

Elle joue un rôle dans la transduction de signal, intervenant dans le métabolisme, l'angiogénèse et la cancérogenèse[1].

Des découvertes récentes ont révélé que la phosphoinositide 3-kinase active la signalisation NF-κB et le copanlisib, un inhibiteur de la phosphoinositide 3-kinase peut bloquer efficacement la double signalisation PI3K/AKT - NF-κB dans les cellules activées du lymphome diffus à grandes cellules B , conduisant à une régression tumorale [2]. L'inhibition du phosphoinositide 3-kinase dans le lymphome diffus à grandes cellules B s'est également avérée diminuer l'activité de NF-κB [3].

Inhibiteurs

L'idélalisib et le copanlisib sont des inhibiteurs de la phosphoinositide 3-kinase, en cours de test dans les leucémies.

Notes et références

  1. a et b Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B, The emerging mechanisms of isoform-specific PI3K signalling, Nat Rev Mol Cell Biol, 2010;11:329-341
  2. Juliane Paul, Maurice Soujon, Antje M. Wengner et Sabine Zitzmann-Kolbe, « Simultaneous Inhibition of PI3Kδ and PI3Kα Induces ABC-DLBCL Regression by Blocking BCR-Dependent and -Independent Activation of NF-κB and AKT », Cancer Cell, vol. 31, no 1,‎ , p. 64–78 (ISSN 1535-6108, DOI 10.1016/j.ccell.2016.12.003, lire en ligne, consulté le )
  3. (en) Wendan Xu, Philipp Berning, Tabea Erdmann et Michael Grau, « mTOR inhibition amplifies the anti-lymphoma effect of PI3Kβ/δ blockage in diffuse large B-cell lymphoma », Leukemia, vol. 37, no 1,‎ , p. 178–189 (ISSN 1476-5551, PMID 36352190, PMCID PMC9883168, DOI 10.1038/s41375-022-01749-0, lire en ligne, consulté le )

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