Teresina Tua, Kniestück, mit Violine

Signatur des Originals: S 36/F10101

Otto Ludwig Sommerstorff als Faust, Teresina Sommerstorff als Gretchen, Rollenbild, Doppelbildnis, in: Johann Wolfgang von Goethe: Faust

Signatur des Originals: S 36/F11156

Teresina Tua, Ganzfigurbildnis, mit Geige

Signatur des Originals: S 36/F11889

Teresina Tua, Ganzfigurbildnis, mit Geige

Signatur des Originals: S 36/F11890

Teresina Sommerstorff, Rollenbild, Brustbild, in: Maurice Maeterlinck: Monna Vanna

Signatur des Originals: S 36/F12414

Teresina Sommerstorff, {[N.N.], Szenenfoto, Doppelbildnis, in: Maurice Maeterlinck: Monna Vanna

Signatur des Originals: S 36/F12417

Teresina Tua, Kniestück

Signatur des Originals: S 36/G02406

Teresina Tua, Kniestück

Signatur des Originals: S 36/G02407

Teresina Tua, Kniestück

Signatur des Originals: S 36/G02408

Robert il Diavolo, Act I., Scene 4 : Alice: Più non vie. Roberto: Che intendo! Ah madre! io gelo. ; Alice: She is no more. Robert: What! my mother? O torture.

Signatur des Originals: S 36/G03301

Teresina Gessner als Hero, Hüftbild, Rollenbild

Signatur des Originals: S 36/F12448

NHERF1 recruits the tumor suppressors PTEN and PHLPP to synergistically inhibit the PI-3K pathway

Glioblastoma multiforme is the most common form of brain cancer that presents patients with a poor prognosis that has remained unchanged over the past few decades. The tumor suppressor phosphatase PTEN antagonizes one of the major oncogenic pathways involved in the progression of glioblastoma, and is frequently deleted in this cancer type. Contrary to our expectations, we found that most glioblastoma cells expressing endogenous PTEN also harbor basal PI-3K/AKT activation mainly attributable to impaired PTEN membrane localization. This alteration correlated with a shift of the adaptor protein NHERF1, which contributes to PTEN membrane recruitment in normal cells, from the membrane to the cytoplasm. In cells expressing membrane-localized NHERF1, only simultaneous PTEN and NHERF1 depletion achieved AKT activation, suggesting the involvement of additional PI-3K/AKT suppressor regulated by NHERF1. We identified these novel interactors of NHERF1 as the PHLPP1 and PHLPP2 phosphatases. ^ NHERF1 directly interacted and recruited both PHLPP proteins to the membrane and, through both NHERF1 PDZ domains, assembled ternary complexes consisting of PTEN-NHERF1-PHLPP. Only simultaneous depletion of PTEN and PHLPP1 significantly activated AKT and increased proliferation in cells with membrane-localized NHERF1. Analysis of glioblastoma human tumors revealed frequent loss of membrane-localized NHERF1. On the other hand, targeting of NHERF1 to the membrane achieved suppression of AKT and cell proliferation. Our findings reveal a novel mechanism for PI-3K/AKT regulation by the synergistic cooperation between two important tumor suppressors, PTEN and PHLPP, via the scaffold protein NHERF1. ^