scholarly journals Keratin 19 interacts with GSK3β to regulate its nuclear accumulation and degradation of cyclin D3

2021 ◽  
Vol 32 (21) ◽  
Author(s):  
Pooja Sharma ◽  
Sarah Tiufekchiev ◽  
Victoria Lising ◽  
Seung Woo Chung ◽  
Jung Soo Suk ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Cyclin D3 ◽  
Glycogen Synthase Kinase ◽  
Nuclear Accumulation ◽  
Glycogen Synthase Kinase 3Β ◽  
Keratin 19

Keratin 19 (K19) inhibits glycogen synthase kinase-3β (GSK3β) accumulation in the nucleus, preventing cyclin D3 degradation. K19 physically interacts with GSK3β, and this interaction requires Ser 10 and 35 of K19. Mutating either residues decreased cyclin D3 levels and cell proliferation. The K19–GSK3β–cyclin D3 pathway also regulates the sensitivity of cancer cells to CDK4/6 inhibitors.

Detection of Active Fraction of Glycogen Synthase Kinase 3β in Cancer Cells by Nonradioisotopic in vitro Kinase Assay

Oncology ◽  
2006 ◽  
Vol 71 (3-4) ◽  
pp. 297-305 ◽  
Author(s):  
Wei Mai ◽  
Katsuyoshi Miyashita ◽  
Abbas Shakoori ◽  
Bin Zhang ◽  
Zhi Wei Yu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Kinase Assay ◽  
Glycogen Synthase Kinase 3Β ◽  
Active Fraction ◽  
In Vitro Kinase Assay

scholarly journals Expression of Cyclooxygenase-2 Is Regulated by Glycogen Synthase Kinase-3β in Gastric Cancer Cells

2005 ◽  
Vol 281 (8) ◽  
pp. 4564-4569 ◽  
Author(s):  
Alexandra Thiel ◽  
Mira Heinonen ◽  
Johanna Rintahaka ◽  
Tuija Hallikainen ◽  
Annabrita Hemmes ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Cyclooxygenase 2 ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Gastric Cancer Cells

scholarly journals Modulation of glycogen synthase kinase-3β following TRAIL combinatorial treatment in cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (41) ◽  
pp. 66892-66905 ◽  
Author(s):  
Sreevidya Santha ◽  
Gantulga Davaakhuu ◽  
Aninda Basu ◽  
Rong Ke ◽  
Subhasis Das ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Combinatorial Treatment

scholarly journals Keratin 19 interacts with GSK3β to regulate its nuclear accumulation and degradation of cyclin D3

2021 ◽  
Author(s):  
Pooja Sharma ◽  
Sarah Tiufekchiev ◽  
Victoria Lising ◽  
Seung Woo Chung ◽  
Jung Soo Suk ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cyclin D3 ◽  
Nuclear Accumulation ◽  
Cyclin Dependent Kinase ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Keratin 19 ◽  
Head Domain ◽  
Cancer Types ◽  
Potential Strategy

Cyclin D3 regulates the G1/S transition and is frequently overexpressed in several cancer types including breast cancer, where it promotes tumor progression. Here, we show that a cytoskeletal protein keratin 19 (K19) physically interacts with a serine/threonine kinase GSK3β and prevents GSK3β-dependent degradation of cyclin D3. The absence of K19 allowed active GSK3β to accumulate in the nucleus and degrade cyclin D3. Specifically, the head domain of K19 was required to sustain inhibitory phosphorylation of GSK3β Ser9, prevent nuclear accumulation of GSK3β, and maintain cyclin D3 levels and cell proliferation. K19 was found to interact with GSK3β and K19-GSK3β interaction was mapped out to require Ser10 and Ser35 residues on the head domain of K19. Unlike wildtype K19, S10A and S35A mutants failed to maintain total and nuclear cyclin D3 levels and induce cell proliferation. Finally, we show that the K19-GSK3β-cyclin D3 pathway affected sensitivity of cells towards inhibitors to cyclin dependent kinase 4 and 6 (CDK4/6). Overall, these findings establish a role for K19 in the regulation of GSK3β-cyclin D3 pathway and demonstrate a potential strategy for overcoming resistance to CDK4/6 inhibitors.

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