Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Abstract The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic...

Full description

Saved in:

Bibliographic Details
Published in:	Drug resistance updates Vol. 10; no. 1; pp. 13 - 29
Main Authors:	Maddika, Subbareddy, Ande, Sudharsana Rao, Panigrahi, Soumya, Paranjothy, Ted, Weglarczyk, Kazimierz, Zuse, Anne, Eshraghi, Mehdi, Manda, Kamala D, Wiechec, Emilia, Los, Marek
Format:	Journal Article
Language:	English
Published:	Scotland Elsevier Ltd 01-02-2007
Subjects:	Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis - physiology apoptosis in-vivo bcl-2 family proteins c-myc Cell cycle Cell Cycle - physiology Cell Death Cell Proliferation Cell survival Cell Survival - physiology Cyclin-Dependent Kinase Inhibitor Proteins - physiology Cyclin-Dependent Kinases - physiology Cyclins - physiology dependent kinases dna-damage Drug Delivery Systems Drug Design element-binding protein forkhead transcription factor gadd45 GADD45, PUMA, NOXA, HIPK2 Hematology, Oncology and Palliative Medicine HipK2 Humans Infectious Disease Neoplasms - drug therapy Neoplasms - physiopathology nf-kappa-b noxa phosphoinositide 3-kinase Proto-Oncogene Proteins c-bcl-2 - physiology PUMA tumor-suppressor Cell survival ANT BH3 MYT1 adenine nucleotide translocator GADD45, PUMA, NOXA, HIPK2 voltage-dependent anion channel Apaf1 Cell death membrane-associated and tyrosine/threonine-specific-1 apoptosis inducing factor Cell cycle MDM2 VDAC bcl2-homology domain 3 apoptosis activating factor 1 AIF mouse double minute 2
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic regulatory circuits. This review highlights some of the connections between opposite-acting pathways. Thus, we discuss the role of cyclins in the apoptotic process, and in the regulation of cell proliferation. CDKs and their inhibitors like the INK4-family (p16Ink4a , p15Ink4b , p18Ink4c , p19Ink4d ), and the Cip1/Waf1/Kip1-2-family (p21Cip1/Waf1 , p27Kip1 , p57Kip2 ) are shown both in the context of proliferation regulators and as contributors to the apoptotic machinery. Bcl2-family members (i.e. Bcl2, Bcl-XL Mcl-1L ; Bax, Bok/Mtd, Bak, and Bcl-XS ; Bad, Bid, BimEL , Bmf, Mcl-1S ) are highlighted both for their apoptosis-regulating capacity and also for their effect on the cell cycle progression. The PI3-K/Akt cell survival pathway is shown as regulator of cell metabolism and cell survival, but examples are also provided where aberrant activity of the pathway may contribute to the induction of apoptosis. Myc/Mad/Max proteins are shown both as a powerful S-phase driving complex and as apoptosis-sensitizers. We also discuss multifunctional proteins like p53 and Rb (RBL1/p107, RBL2/p130) both in the context of G1 -S transition and as apoptotic triggers. Finally, we reflect on novel therapeutic approaches that would involve redirecting over-active survival and proliferation pathways towards induction of apoptosis in cancer cells.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1368-7646 1532-2084 1532-2084
DOI:	10.1016/j.drup.2007.01.003