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?-TrCP1 Is a Vacillatory Regulator of Wnt Signaling.

ABSTRACT: Simultaneous hyperactivation of Wnt and antioxidant response (AR) are often observed during oncogenesis. However, it remains unclear how the ?-catenin-driven Wnt and the Nrf2-driven AR mutually regulate each other. The situation is compounded because many players in these two pathways are redox sensors, rendering bolus redox signal-dosing methods uninformative. Herein we examine the ramifications of single-protein target-specific AR upregulation in various knockdown lines. Our data document that Nrf2/AR strongly inhibits ?-catenin/Wnt. The magnitude and mechanism of this negative regulation are dependent on the direct interaction between ?-catenin N terminus and ?-TrCP1 (an antagonist of both Nrf2 and ?-catenin), and independent of binding between Nrf2 and ?-TrCP1. Intriguingly, ?-catenin positively regulates AR. Because AR is a negative regulator of Wnt regardless of ?-catenin N terminus, this switch of function is likely sufficient to establish a new Wnt/AR equilibrium during tumorigenesis.

SUBMITTER: Long MJ

PROVIDER: S-EPMC5634333 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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β-TrCP1 Is a Vacillatory Regulator of Wnt Signaling.

Long Marcus John MJ Lin Hong-Yu HY Parvez Saba S Zhao Yi Y Poganik Jesse Richard JR Huang Paul P Aye Yimon Y

Cell chemical biology 20170720 8

Simultaneous hyperactivation of Wnt and antioxidant response (AR) are often observed during oncogenesis. However, it remains unclear how the β-catenin-driven Wnt and the Nrf2-driven AR mutually regulate each other. The situation is compounded because many players in these two pathways are redox sensors, rendering bolus redox signal-dosing methods uninformative. Herein we examine the ramifications of single-protein target-specific AR upregulation in various knockdown lines. Our data document that ...[more]

PMID: 28736239

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