Inverse Relationship Between Skp2 Ubiquitin Ligase and the Cyclin Dependent Kinase Inhibitor p27 Kip1 in Prostate Cancer

2003 ◽  
Vol 170 (1) ◽  
pp. 241-245 ◽  
Author(s):  
OFER BEN-IZHAK ◽  
SHIRLY LAHAV-BARATZ ◽  
SHIMON MERETYK ◽  
SHOSHANA BEN-ELIEZER ◽  
EDMOND SABO ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ubiquitin Ligase ◽  
Inverse Relationship ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
P27 Kip1

scholarly journals FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27 Kip1 in acute myeloid leukemia

Haematologica ◽  
2017 ◽  
Vol 102 (8) ◽  
pp. 1378-1389 ◽  
Author(s):  
Ines Peschel ◽  
Silvio R. Podmirseg ◽  
Martin Taschler ◽  
Justus Duyster ◽  
Katharina S. Götze ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
P27 Kip1 ◽  
Acute Myeloid

scholarly journals The CRL4Cdt2 Ubiquitin Ligase Mediates the Proteolysis of Cyclin-Dependent Kinase Inhibitor Xic1 through a Direct Association with PCNA

2010 ◽  
Vol 30 (17) ◽  
pp. 4120-4133 ◽  
Author(s):  
Dong Hyun Kim ◽  
Varija N. Budhavarapu ◽  
Carlos R. Herrera ◽  
Hyung Wook Nam ◽  
Yu Sam Kim ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Proliferating Cell Nuclear Antigen ◽  
Kinase Inhibitor ◽  
Binding Domain ◽  
Nuclear Antigen ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Terminal Domain ◽  
Lysine Residues ◽  
Proliferating Cell

ABSTRACT During DNA polymerase switching, the Xenopus laevis Cip/Kip-type cyclin-dependent kinase inhibitor Xic1 associates with trimeric proliferating cell nuclear antigen (PCNA) and is recruited to chromatin, where it is ubiquitinated and degraded. In this study, we show that the predominant E3 for Xic1 in the egg is the Cul4-DDB1-XCdt2 (Xenopus Cdt2) (CRL4Cdt2) ubiquitin ligase. The addition of full-length XCdt2 to the Xenopus extract promotes Xic1 turnover, while the N-terminal domain of XCdt2 (residues 1 to 400) cannot promote Xic1 turnover, despite its ability to bind both Xic1 and DDB1. Further analysis demonstrated that XCdt2 binds directly to PCNA through its C-terminal domain (residues 401 to 710), indicating that this interaction is important for promoting Xic1 turnover. We also identify the cis-acting sequences required for Xic1 binding to Cdt2. Xic1 binds to Cdt2 through two domains (residues 161 to 170 and 179 to 190) directly flanking the Xic1 PCNA binding domain (PIP box) but does not require PIP box sequences (residues 171 to 178). Similarly, human p21 binds to human Cdt2 through residues 156 to 161, adjacent to the p21 PIP box. In addition, we identify five lysine residues (K180, K182, K183, K188, and K193) immediately downstream of the Xic1 PIP box and within the second Cdt2 binding domain as critical sites for Xic1 ubiquitination. Our studies suggest a model in which both the CRL4Cdt2 E3- and PIP box-containing substrates, like Xic1, are recruited to chromatin through independent direct associations with PCNA.

scholarly journals Deregulation of the Rho GTPase, Rac1, suppresses cyclin-dependent kinase inhibitor p21CIP1 levels in androgen-independent human prostate cancer cells

Oncogene ◽  
2004 ◽  
Vol 23 (32) ◽  
pp. 5513-5522 ◽  
Author(s):  
Selena Knight-Krajewski ◽  
Catherine F Welsh ◽  
YunQi Liu ◽  
Leah S Lyons ◽  
Joanne M Faysal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Rho Gtpase ◽  
Kinase Inhibitor ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Cyclin Dependent Kinase ◽  
Prostate Cancer Cells ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Androgen Independent
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