TY - JOUR
T1 - New Insights into CDK Regulators
T2 - Novel Opportunities for Cancer Therapy
AU - Bury, Marina
AU - Le Calvé, Benjamin
AU - Ferbeyre, Gerardo
AU - Blank, Volker
AU - Lessard, Frédéric
N1 - Funding Information:
M.B. was supported by a Télévie fellowship (FNRS, Belgium). V.B. acknowledges grants from the Canadian Institutes of Health Research (CIHR, Canada) MOP-97932 and PJT-152937. G.F. acknowledges CCSRI (Canadian Cancer Society Research Institute: 704223) and the CIBC Chair for Breast Cancer Research at the CR-CHUM. We have no conflicts of interest to declare.
Funding Information:
M.B. was supported by a Télévie fellowship (FNRS, Belgium). V.B. acknowledges grants from the Canadian Institutes of Health Research (CIHR, Canada) MOP-97932 and PJT-152937. G.F. acknowledges CCSRI (Canadian Cancer Society Research Institute: 704223) and the CIBC Chair for Breast Cancer Research at the CR-CHUM.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/5
Y1 - 2021/5
N2 - Cyclins and their catalytic partners, the cyclin-dependent kinases (CDKs), control the transition between different phases of the cell cycle. CDK/cyclin activity is regulated by CDK inhibitors (CKIs), currently comprising the CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family and the inhibitor of kinase (INK) family. Recent studies have identified a third group of CKIs, called ribosomal protein-inhibiting CDKs (RPICs). RPICs were discovered in the context of cellular senescence, a stable cell cycle arrest with tumor-suppressing abilities. RPICs accumulate in the nonribosomal fraction of senescent cells due to a decrease in rRNA biogenesis. Accordingly, RPICs are often downregulated in human cancers together with other ribosomal proteins, the tumor-suppressor functions of which are still under study. In this review, we discuss unique therapies that have been developed to target CDK activity in the context of cancer treatment or senescence-associated pathologies, providing novel tools for precision medicine.
AB - Cyclins and their catalytic partners, the cyclin-dependent kinases (CDKs), control the transition between different phases of the cell cycle. CDK/cyclin activity is regulated by CDK inhibitors (CKIs), currently comprising the CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family and the inhibitor of kinase (INK) family. Recent studies have identified a third group of CKIs, called ribosomal protein-inhibiting CDKs (RPICs). RPICs were discovered in the context of cellular senescence, a stable cell cycle arrest with tumor-suppressing abilities. RPICs accumulate in the nonribosomal fraction of senescent cells due to a decrease in rRNA biogenesis. Accordingly, RPICs are often downregulated in human cancers together with other ribosomal proteins, the tumor-suppressor functions of which are still under study. In this review, we discuss unique therapies that have been developed to target CDK activity in the context of cancer treatment or senescence-associated pathologies, providing novel tools for precision medicine.
KW - CDK
KW - CDK regulators
KW - cell cycle
KW - cyclin
KW - ribosomal proteins
KW - RPIC
UR - http://www.scopus.com/inward/record.url?scp=85101999799&partnerID=8YFLogxK
U2 - 10.1016/j.tcb.2021.01.010
DO - 10.1016/j.tcb.2021.01.010
M3 - Review article
C2 - 33676803
AN - SCOPUS:85101999799
SN - 0962-8924
VL - 31
SP - 331
EP - 344
JO - Trends in Cell Biology
JF - Trends in Cell Biology
IS - 5
ER -
