Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma

Low levels of p27Kip1 are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27Kip1 for degradation, was overexpressed and was inversely related to p27Kip1 levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2‐dependent p27 degradation was recently discovered, but its role in human malignancies is unknown.

[1]  Michele Pagano,et al.  SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27 , 1999, Nature Cell Biology.

[2]  J. Slingerland,et al.  The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer. , 1999, Annual review of medicine.

[3]  M. Stanley,et al.  Overexpression of Skp2 in carcinoma of the cervix does not correlate inversely with p27 expression , 2003, International journal of cancer.

[4]  Brett Larsen,et al.  The cell-cycle regulatory protein Cks1 is required for SCFSkp2-mediated ubiquitinylation of p27 , 2001, Nature Cell Biology.

[5]  Jiri Bartek,et al.  p27 destruction: Cks1 pulls the trigger , 2001, Nature Cell Biology.

[6]  Wilhelm Krek,et al.  p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells , 1999, Nature Cell Biology.

[7]  J Wade Harper,et al.  Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  Michele Pagano,et al.  Inverse relation between levels of p27Kip1 and of its ubiquitin ligase subunit Skp2 in colorectal carcinomas , 2001, Cancer.

[9]  S. Reed,et al.  The Saccharomyces cerevisiae CKS1 gene, a homolog of the Schizosaccharomyces pombe suc1+ gene, encodes a subunit of the Cdc28 protein kinase complex , 1989, Molecular and cellular biology.

[10]  J. Mestan,et al.  Skp2 is oncogenic and overexpressed in human cancers , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  James M. Roberts,et al.  CDK inhibitors: positive and negative regulators of G1-phase progression. , 1999, Genes & development.

[12]  R. Deshaies.  SCF and Cullin/Ring H2-based ubiquitin ligases. , 1999, Annual review of cell and developmental biology.

[13]  S. Sato,et al.  High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas. , 2001, Cancer research.

[14]  H Strohmaier,et al.  A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1. , 2001, Molecular cell.

[15]  M. Kitagawa,et al.  High expression of Cks1 in human non-small cell lung carcinomas. , 2003, Biochemical and biophysical research communications.

[16]  P. Beer-Romero,et al.  Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. , 1995, Science.

[17]  S. Ramaswamy,et al.  Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. , 2002, The Journal of clinical investigation.