Cellular and Molecular Life Sciences

, Volume 67, Issue 21, pp 3589–3608 | Cite as

Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment

  • Gianluca Tell
  • Damiano Fantini
  • Franco Quadrifoglio
Multi-Author Review

Abstract

The apurinic endonuclease 1/redox factor-1 (APE1) has a crucial function in DNA repair and in redox signaling in mammals, and recent studies identify it as an excellent target for sensitizing tumor cells to chemotherapy. APE1 is an essential enzyme in the base excision repair pathway of DNA lesions caused by oxidation and alkylation. As importantly, APE1 also functions as a redox agent maintaining transcription factors involved in cancer promotion and progression in an active reduced state. Very recently, a new unsuspected function of APE1 in RNA metabolism was discovered, opening new perspectives for this multifunctional protein. These observations underline the necessity to understand the molecular mechanisms responsible for fine-tuning its different biological functions. This survey intends to give an overview of the multifunctional roles of APE1 and their regulation in the context of considering this protein a promising tool for anticancer therapy.

Keywords

Base excision repair Oxidative stress Redox signalling Nucleolus Cancer 

Abbreviations

8-OHG

8-Hydroxyguanine

AP

Apurinic/apyrimidinic

AP-1

Activating Protein-1

APE1

Apurinic apyrimidinic endonuclease 1

BER

Base excision repair

CKI and CKII

Casein kinase I and II

CREB

cAMP-responsible element binding protein

Egr-1

Early growth response protein-1

FEN1

Flap endonuclease I

GSK3

Glycogen synthase kinase 3

GzmA

Granzyme A

GzmK

Granzyme K

HIF-1α

Hypoxia inducible factor-1α

MTS

Mitochondrial targeting sequence

MPG

Methylpurine DNA glycosylase

MYH

Human MutY glycosylase homolog

NF-κB

Nuclear factor-kappaB

nCaRE

Negative calcium responsive elements

NLS

Nuclear localization signal

NPM1

Nucleophosmin 1

OGG-1

8-Oxoguanine DNA glycosylase

PARP-1

Poly(ADP-ribose) polymerase

Pax

Paired box-containing proteins

PCNA

Proliferating cell nuclear antigen

PEBP-2

Polyoma virus enhancer-binding protein-2

PKC

Protein kinase C

Polβ

Polymerase β

PTEN

Phosphatase and tensin homolog

PTH

Parathyroid hormone

PTM

Post-translational modification

RFC

Replication factor C

ROS

Reactive oxygen species

Trx

Thioredoxin

XRCC1

X-ray cross-species complementing 1

Notes

Acknowledgments

We thank Dr. Mark R. Kelley for helpful discussions. This work was supported by grants from: MIUR (FIRB RBRN07BMCT_008 and PRIN 2008CCPKRP_003) and from MAE (Joint Mobility Projects Program 2008–2010) to G.T.

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Gianluca Tell
    • 1
  • Damiano Fantini
    • 1
  • Franco Quadrifoglio
    • 1
  1. 1.Department of Biomedical Sciences and TechnologiesUniversity of UdineUdineItaly

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