TITLE:
Cks1: Structure, Emerging Roles and Implications in Multiple Cancers
AUTHORS:
Vinayak Khattar, Jaideep V. Thottassery
KEYWORDS:
Cks1; Cks2; Skp2; Cdk1; p27; Kip1; p130; Rb2; CKI; Ubiquitination; Proteasome; ERK1/2
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.8,
October
29,
2013
ABSTRACT: Deregulation
of the cell cycle results in loss of normal control mechanisms that prevent
aberrant cell proliferation and cancer progression. Regulation of the cell
cycle is a highly complex process with many layers of control. One of these
mechanisms involves timely degradation of CDK inhibitors (CKIs) like p27Kip1 by the ubiquitin proteasomal system (UPS). Cks1 is a 9 kDa protein which is
frequently overexpressed in different tumor subtypes, and has pleiotropic roles
in cell cycle progression, many of which remain to be fully characterized. One
well characterized molecular role of Cks1 is that of an essential adaptor that
regulates p27Kip1 abundance by facilitating its interaction with the
SCF-Skp2 E3 ligase which appends ubiquitin to p27Kip1 and targets it
for degradation through the UPS. In addition, emerging research has uncovered
p27Kip1-independent roles of Cks1 which have provided crucial
insights into how it may be involved in cancer progression. We review here the
structural features of Cks1 and their functional implications, and also some recently
identified Cks1 roles and their involvement in breast and other cancers.