Regulation of Cdk7 activity through a phosphatidylinositol (3)-kinase/PKC-ι-mediated signaling cascade in glioblastoma

Carcinogenesis
S DesaiM Acevedo-Duncan

Abstract

The objective of this research was to study the potential function of protein kinase C (PKC)-ι in cell cycle progression and proliferation in glioblastoma. PKC-ι is highly overexpressed in human glioma and benign and malignant meningioma; however, little is understood about its role in regulating cell proliferation of glioblastoma. Several upstream molecular aberrations and/or loss of PTEN have been implicated to constitutively activate the phosphatidylinositol (PI) (3)-kinase pathway. PKC-ι is a targeted mediator in the PI (3)-kinase signal transduction repertoire. Results showed that PKC-ι was highly activated and overexpressed in glioma cells. PKC-ι directly associated and phosphorylated Cdk7 at T170 in a cell cycle-dependent manner, phosphorylating its downstream target, cdk2 at T160. Cdk2 has a major role in inducing G(1)-S phase progression of cells. Purified PKC-ι phosphorylated both endogenous and exogenous Cdk7. PKC-ι downregulation reduced Cdk7 and cdk2 phosphorylation following PI (3)-kinase inhibition, phosphotidylinositol-dependent kinase 1 knockdown as well as PKC-ι silencing (by siRNA treatment). It also diminished cdk2 activity. PKC-ι knockdown inhibited overall proliferation rates and induced apoptosis in gliom...Continue Reading

References

Sep 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·T AkiyamaK Toyoshima
Jan 1, 1968·Acta Pathologica Et Microbiologica Scandinavica·J Pontén, E H Macintyre
Aug 15, 1983·The Biochemical Journal·J S Davis, M R Clark
Nov 5, 1997·The Journal of Biological Chemistry·N R Murray, A P Fields
Aug 8, 1998·Genes & Development·N Dyson
Nov 9, 2004·Structure·Graziano LolliLouise N Johnson
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Apr 13, 2005·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Hiroko Ohgaki
May 4, 2005·Current Neurology and Neuroscience Reports·Santosh KesariPatrick Y Wen
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Astrid M EderGordon B Mills
Oct 6, 2005·Cancer Research·Roderick P RegalaAlan P Fields
Oct 13, 2005·Journal of Cell Science·Barry J CollinsDario R Alessi
Dec 22, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Ciro ParlatoAldo Moraci
Mar 22, 2007·Proteins·Graziano Lolli, Louise N Johnson
Jun 1, 2007·Cellular Signalling·Alakananda Basu, Usha Sivaprasad
Jan 24, 2008·Cell Proliferation·R PatelM Acevedo-Duncan
Oct 14, 2008·Genome Biology·Yong ChiBruce E Clurman
Sep 8, 2010·Molecular Cancer·R Mitchell BaldwinIan A J Lorimer
Feb 15, 2011·The International Journal of Biochemistry & Cell Biology·Prajit PillaiMildred Acevedo-Duncan

❮ Previous
Next ❯

Citations

Jun 27, 2014·Neurochemical Research·Andrea N McCrayMildred Acevedo-Duncan
Aug 3, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sujie NiRunzhou Ni
May 10, 2020·Cancer Metastasis Reviews·Georgina P SavaSimak Ali
Dec 8, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·S M Anisul IslamMildred Acevedo-Duncan
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tahir Ali ChohanMuhammad Sajid Hamid Akash
Jun 18, 2021·Journal of Cell Science·Melisa J AndradeKapaettu Satyamoorthy

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis