Phosphorylation and isoform use in p120-catenin during development and tumorigenesis

Hong, Ji Yeon; Oh, Il‐Hoan; McCrea, Pierre D.

doi:10.1016/j.bbamcr.2015.10.008

Cited by 30 publications

(41 citation statements)

References 160 publications

(313 reference statements)

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“…While several modifications have been described for members of the p120ctn family [30,55,81,82], the functional consequences of these modifications are incompletely understood.…”

Section: Posttranslational Modificationsmentioning

confidence: 99%

“…Although multiple phosphorylation sites have been identified in other p120ctnfamily members [38,82], however, it is still unclear if these modifications occur in central neurons and if they have functional consequences.…”

Section: Posttranslational Modificationsmentioning

confidence: 99%

“…The grey regions indicate phosphorylation enriched regions before (region A) and after the ARM domains (region B) in each protein. Reference ID: 1, [30]; 2, [82]; 3, [27]; 4, [83]; 5, [84]; 6, [31]; 7, [53]; 8, combination of [29,54,75,81,85]; Ub, [87]; Palm: [19]. The reference protein sequences and region of the ARM repeats are as in Fig.…”

Section: Figmentioning

confidence: 99%

“…Multiple forms of each protein are generated by several mechanisms, including use of alternative translational start sites [11,13], splice variants, proteolysis [20,21] and posttranslational modifications [19,22]. Alternative translational start sites have been described for p120ctn and ARVCF [11,13], leading to differences in the composition of the N-terminal region.…”

Section: Introductionmentioning

confidence: 99%

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Functional roles of p120ctn family of proteins in central neurons

Arikkath

2017

Seminars in Cell & Developmental Biology

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The cadherin-catenin complex in central neurons is associated with a variety of cytosolic partners, collectively called catenins. The p120ctn members are a family of catenins that are distinct from the more ubiquitously expressed α- and β-catenins. It is becoming increasingly clear that the functional roles of the p120ctn family of catenins in central neurons extend well beyond their functional roles in non-neuronal cells in partnering with cadherin to regulate adhesion. In this review, we will provide an overview of the p120ctn family in neurons and their varied functional roles in central neurons. Finally, we will examine the emerging roles of this family of proteins in neurodevelopmental disorders.

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“…While several modifications have been described for members of the p120ctn family [30,55,81,82], the functional consequences of these modifications are incompletely understood.…”

Section: Posttranslational Modificationsmentioning

confidence: 99%

Section: Posttranslational Modificationsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Functional roles of p120ctn family of proteins in central neurons

Arikkath

2017

Seminars in Cell & Developmental Biology

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“…There is growing interest in p120‐catenin and its role in cancer etiology . As a member of the Armadillo family, p120‐catenin is a key component of the adherens junction (AJ), with links to cell‐cell interactions and signaling within the nucleus . Cell adhesion and signaling functions have been defined for other AJ members, including β‐catenin and E‐cadherin .…”

Section: Introductionmentioning

confidence: 99%

Divergent roles of p120‐catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen‐induced rat skin tumors

Wang

Chen

Dashwood

et al. 2017

Molecular Carcinogenesis

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The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) targets multiple organs for tumorigenesis in the rat, including the colon and the skin. PhIP-induced skin tumors were subjected to mutation screening, which identified genetic changes in Hras (7/40, 17.5%) and Tp53 (2/40, 5%), but not in Ctnnb1, a commonly mutated gene in PhIP-induced colon tumors. Despite the absence of Ctnnb1 mutations, β-catenin was overexpressed in nuclear and plasma membrane fractions from PhIP-induced skin tumors, coinciding with loss of p120-catenin from the plasma membrane, and the appearance of multiple p120-catenin-associated bands in the nuclear extracts. Real-time RT-PCR revealed that p120-catenin isoforms 1 and 4 were upregulated in PhIP-induced skin tumors, whereas p120-catenin isoform 3 was expressed uniformly, compared with adjacent normal-looking tissue. In human epidermoid carcinoma and colon cancer cells, transient transfection of p120-catenin isoform 1A enhanced the viability and cell invasion index, whereas transient transfection of p120-catenin isoform 4A increased cell viability and cell proliferation. Knockdown of p120-catenin revealed a corresponding reduction in the expression of β-catenin and a transcriptionally regulated target, Ccnd1/Cyclin D1. Co-immunoprecipitation experiments identified associations of β-catenin with p120-catenin isoforms in PhIP-induced skin tumors and human cancer cell lines. The results are discussed in the context of therapeutic strategies that might target different p120-catenin isoforms, providing an avenue to circumvent constitutively active β-catenin arising via distinct mechanisms in skin and colon cancer.

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CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions

Herrera-Pariente,

Bonjoch,

Muñoz

et al. 2024

Gastric Cancer

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Background CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). Methods After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed β-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. Results Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. Conclusions Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.

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Phosphorylation and isoform use in p120-catenin during development and tumorigenesis

Cited by 30 publications

References 160 publications

Functional roles of p120ctn family of proteins in central neurons

Functional roles of p120ctn family of proteins in central neurons

Divergent roles of p120‐catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen‐induced rat skin tumors

CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions

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