scholarly journals Two Degradation Pathways of the p35 Cdk5 (Cyclin-dependent Kinase) Activation Subunit, Dependent and Independent of Ubiquitination

2015 ◽  
Vol 291 (9) ◽  
pp. 4649-4657 ◽  
Author(s):  
Toshiyuki Takasugi ◽  
Seiji Minegishi ◽  
Akiko Asada ◽  
Taro Saito ◽  
Hiroyuki Kawahara ◽  
...  
Keyword(s):  
Degradation Pathways ◽  
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

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 Clb5-associated Kinase Activity is Required Early in the Spindle Pathway for Correct Preanaphase Nuclear Positioning in Saccharomyces cerevisiae

1998 ◽  
Vol 143 (1) ◽  
pp. 135-145 ◽  
Author(s):  
Marisa Segal ◽  
Duncan J. Clarke ◽  
Steven I. Reed
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Phase Transitions ◽  
Room Temperature ◽  
Kinase Activity ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Nuclear Positioning ◽  
Spindle Positioning ◽  
Kinase Activation ◽  
M Phase

In Saccharomyces cerevisiae, a single cyclin-dependent kinase, Cdc28, regulates both G1/S and G2/M phase transitions by associating with stage-specific cyclins. During progression through S phase and G2/M, Cdc28 is activated by the B-type cyclins Clb1–6. Because of functional redundancy, specific roles for individual Clbs have been difficult to assign. To help genetically define such roles, strains carrying a cdc28ts allele, combined with single CLB deletions were studied. We assumed that by limiting the activity of the kinase, these strains would be rendered more sensitive to loss of individual Clbs. By this approach, a novel phenotype associated with CLB5 mutation was observed. Homozygous cdc28-4ts clb5 diploids were inviable at room temperature. Cells were defective in spindle positioning, leading to migration of undivided nuclei into the bud. Occasionally, misplaced spindles were observed in cdc28-4 clb5 haploids; additional deletion of CLB6 caused full penetrance. Thus, CLB5 effects proper preanaphase spindle positioning, yet the requirement differs in haploids and diploids. The execution point for the defect corresponded to the time of Clb5-dependent kinase activation. Nevertheless, lethality of cdc28-4 clb5 diploids was not rescued by CLB2 or CLB4 overexpression, indicating a specificity of Clb5 function beyond temporality of expression.

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