Paul , D. and Rapole , S. and Santra , MK. (2021) A new player in an old story: FBXO16 prevents breast cancer tumorigenesis through disrupting cellular function of nuclear β-Catenin. Journal of Experimental Pathology, 1 (1). pp. 22-27.

Text 67.-1. Dr. Manas S. (J Exp Path) open access.pdf Restricted to Repository staff only Download (327Kb) | Request a copy

Abstract

Aberrant nuclear accumulation of β-catenin is associated with cancer pathogenesis; however, the regulation of nuclear β-catenin was largely remained elusive. In J. Pathology, Paul et al. elucidated the molecular mechanism of accumulation of nuclear β-catenin in cancer [1]. β-Catenin is the central modulator of the canonical Wnt signaling pathway. Upon Wnt on state, β-Catenin is translocated to the nucleus and function as a transcription coactivator for several oncogenes. In Wnt off state, β-catenin is mostly localized in the cytoplasm and sequestered by the destruction complex, the negative regulator of β-catenin expression [2,3]. This destruction complex is composed of adenomatous polyposis coli (APC), casein kinase 1α (CK1α), glycogen synthase kinase 3α/β (GSK-3α/β), and AXIN1 [4-8]. CK1α initiates the degradation process of β-Catenin by phosphorylating it at Ser45, which is subsequently phosphorylated at Thr41, Ser37, and Ser33 by GSK3β [9]. The phosphorylated β-catenin is then polyubiquitinated by SCFβ-TrCP to promote its proteasomal degradation. In contrast, in the case of Wnt on state, β-catenin is released from the destruction complex and translocate to the nucleus. It is also reported that Norrin and R-Spondin activate Wnt signaling in stem cells and this activation is Wnt ligand independent [10-12]. They bind to LRP5/6 receptor and prevent the inactivation of LRP function by Rnf43/Znrf3. LRP5/6 functions as a coreceptor of Frizzled receptor and helps to separate Axin from the destruction complex. Thus, they help to translocate β-catenin in the nucleus through sequestration of Axin in the membrane. In the nucleus, β-catenin functions as a transcriptional coactivator to relate plethora of genes.

Item Type:	Article
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	24 Nov 2021 10:29
Last Modified:	26 Nov 2021 12:10
URI:	http://nccs.sciencecentral.in/id/eprint/1079

Actions (login required)

View Item