scholarly journals Structural basis of divergent cyclin‐dependent kinase activation by Spy1/ RINGO proteins

2017 ◽  
Vol 36 (15) ◽  
pp. 2251-2262 ◽  
Author(s):  
Denise A McGrath ◽  
Bre‐Anne Fifield ◽  
Aimee H Marceau ◽  
Sarvind Tripathi ◽  
Lisa A Porter ◽  
...  
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation

Structural basis of cyclin-dependent kinase activation by phosphorylation

1996 ◽  
Vol 3 (8) ◽  
pp. 696-700 ◽  
Author(s):  
Alicia A. Russo ◽  
Philip D. Jeffrey ◽  
Nikola P. Pavletich
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation

scholarly journals Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Patricia Sanmartín-Salinas ◽  
Luis G. Guijarro
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Cultured Cells ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation ◽  
Tnm System ◽  
Protein Levels ◽  
Receptor Signalling ◽  
T Values

We reported that insulin receptor substrate 4 (IRS-4) levels increased in tissue from colorectal cancer (CRC) patients and promoted retinoblastoma-cyclin-dependent kinase activation. The aim of the present study was to evaluate the effect of IRS-4 on IGF-1 receptor pathway and its impact on procaspase 3 and PARP expression in RKO and HepG2 cancer cell lines. The results obtained in vitro were compared with those obtained from biopsies of patients with CRC (n = 18), tubulovillous adenomas (TA) (n = 2) and in matched adjacent normal colorectal (MANC) tissue (n = 20). IRS-4 overexpression in cultured cells induced the overactivation of IGF-1/BRK/AKT/GSK-3/β-catenin/cyclin D1 pathways, which led to increased expression of procaspase 3 and PARP protein levels. Studies carried out on CRC and TA tissues revealed the overactivation of the IGF-1 receptor signalling pathway, as well as the overexpression of procaspase 3 and PARP in tumoural tissue with respect to MANC tissue. The upregulation of IRS-4 in tumoural samples correlated significantly with the increase in pIGF-1 receptor (Tyr 1165/1166) (r = 0.84; p < 0.0001), procaspase 3 (r = 0. 77; p < 0. 0005) and PARP (r = 0. 89; p < 0. 0005). Similarly, we observed an increase in the proteolysis of procaspase 3 in tumoural tissue with respect to MANC tissue, which correlated significantly with the degradation of PARP (r = 0.86; p < 0.0001), p53 (r = 0.84; p < 0.0001), and GSK-3 (r = 0.78; p < 0.0001). The stratification of patient samples using the TNM system revealed that procaspase 3 and caspase 3 increased gradually with T values, which suggests their involvement in the size and local invasion of primary tumours. Taken together, our findings suggest that IRS-4 overexpression promotes the activation of the IGF-1 receptor pathway, which leads to the increase in procaspase 3 levels in CRC.

Insulin receptor substrate-4 is overexpressed in colorectal cancer and promotes retinoblastoma–cyclin-dependent kinase activation

2018 ◽  
Vol 53 (8) ◽  
pp. 932-944 ◽  
Author(s):  
Patricia Sanmartín-Salinas ◽  
María del Val Toledo Lobo ◽  
Fernando Noguerales-Fraguas ◽  
Miguel Toro Londoño ◽  
Antonio Jiménez-Ruiz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation

Structural Basis of the Interaction of Cyclin-Dependent Kinase 2 with Roscovitine and Its Analogues Having Bioisosteric Central Heterocycles

ChemPhysChem ◽  
2017 ◽  
Vol 18 (7) ◽  
pp. 785-795 ◽  
Author(s):  
Michaela Nekardová ◽  
Ladislava Vymětalová ◽  
Prashant Khirsariya ◽  
Silvia Kováčová ◽  
Michaela Hylsová ◽  
...  
Keyword(s):  
Structural Basis ◽  
Cyclin Dependent Kinase
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