Abstract

The Adenoviral E1B-55k Protein Present in HEK293 Cells Mediates Abnormal Accumulation of Key WNT Signaling Proteins in Large Cytoplasmic Aggregates

Highlights

  • IntroductionThe WNT/β-catenin signaling pathway plays a pivotal role during development, organogenesis, stem cell maintenance and self-renewal of many tissues, and aberrant

  • We show that while β-catenin is predominantly localized at the cell membrane, AXIN1, APC, DVL2 and TNKS all co-localize in large cytoplasmic aggregates that are enclosed by a narrow layer of the adenoviral E1B-55k protein present in HEK293 cells

  • We showed that in HEK293 cells central components of the WNT/βcatenin signaling pathway display atypical cellular localizations by being sequestered in large cytoplasmic E1B-55k aggregates

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Summary

Introduction

The WNT/β-catenin signaling pathway plays a pivotal role during development, organogenesis, stem cell maintenance and self-renewal of many tissues, and aberrant. WNT/β-catenin signaling activity is associated with the development of several disease conditions including cancer [1,2]. The main determinant of WNT/β-catenin signaling activity is the level of free cytoplasmic β-catenin that can translocate to the nucleus and activate target genes through interactions of β-catenin with transcription factors of the TCF/LEF family [3]. In cells with low WNT/β-catenin signaling activity, the level of cytoplasmic βcatenin is kept low by the constant action of a degradosome that targets cytosolic β-catenin (by phosphorylation and ubiquitination) for proteolytic degradation. The degradosome comprises in its core of the structural protein APC, the rate limiting structural proteins

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