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Predicting E3 Ubiquitin Ligases as Possible Promising Biomarkers for Brain Tumors

  • Vibhuti Joshi
  • Arun Upadhyay
  • Ayeman Amanullah
  • Ribhav Mishra
  • Amit MishraEmail author
Chapter

Abstract

Cells perform several post-translational changes in various proteins prior to allow their participation in various intracellular metabolic mechanisms. Ubiquitylation is also a post-translational process for different cellular proteins after which modified proteins contribute their physiological functions in distinct cellular processes. E3 ubiquitin ligases are important components of ubiquitin proteasome system (UPS), which specifically recognize critical substrate proteins (abnormal, over-accumulated & old) for their intracellular elimination. Loss of cell cycle regulation is one of the chief possible causes of deregulated cellular proliferation and cancer progression. How different E3 ubiquitin ligases play essential roles in cell-cycle regulation is still one of the unsolved fundamental questions and potentially stands for the development of early diagnostic methods, which can generate new molecular strategies to treat cancer. In this chapter, our main focus is to understand the functions of E3 Ubiquitin Ligases as setting potential biomarker or targets in various cancers and linked with regulatory roles of cell-cycle transitions. The chief objective of this current chapter is to understand the critical requirement of new biomarkers, which can early indicate improper cellular proliferation and cancer progression due to the complex defects in various signal transduction mechanisms linked with the promotion and progress of each phase of the cell cycle. A better understanding of E3 ubiquitin ligases may result in new insights and therapeutic strategies for the treatment and suppression of the development of cancer.

Keywords

E3 ubiquitin ligases Brain tumors Biomarkers Cancer 

Abbreviations

AIP4

Atrophin-1 interacting protein 4

APC/C

Anaphase promoting complex/cyclosome;

BCA2

Breast cancer associated protein 2

BMP

Bone morphogenic protein

BRCA 1

Breast cancer gene 1

c-Cbl

Casitas B- lineage lymphoma

Cdc4

Cell division control protein 4

CHIP

Carboxy terminus of Hsp70-interacting protein

CRLs

Cullin-RING ubiquitin ligases

E6-AP

E6-associated protein

GC

Gas chromatography

Gp78

Glycoprotein 78

HCC

Hepatocellular carcinoma

HECT

Homologous to E6-associated protein C-terminus

HPV

Human papilloma virus

IAPs

Inhibitors of apoptosis protein

IHC

Immunohistochemistry

KRAS

Kirsten rat sarcoma viral oncogene homolog

LATS1

Large tumor suppressor kinase 1

LC3

Light chain 3

MALDI

Matrix assisted laser desorption/ionization

MDM2

Mouse double minute 2

MIC-1

Macrophage inhibitory cytokine-1

NCT

Neoadjuvant chemotherapy

NEDD4

Neural precursor cell expressed developmentally downregulated 4

PEP

Protein elution plate

PHD

Plant homeodomain

PQC

Protein quality control

PTK

Protein tyrosine kinase

RBR

RING-in-between-RING

RING

Really interesting new gene

RT-PCR

Reverse transcriptase-polymerase chain reaction

SCF

Skp1, Cullins and F-box complex

Siah2

Seven in absentia homolog 2

Smad4

S-Mothers against decapentaplegic homolog 4

Smurf 1/2

Smad ubiquitin regulatory factors

TGF-β

Transforming growth factor-β

TNF-α

Tumor necrosis factor-α

TRIM2

Tripartite motif containing 2

TRIM25

Tripartite motif containing 25

UBE2C

Ubiquitin conjugating enzyme 2C

ULK1

Unc-51 like autophagy activating kinase 1

UPS

Ubiquitin proteasome system

XIAP

X-chromosome-linked IAP

Notes

Acknowledgement

In this work, VJ and AU were supported by a research fellowship from University Grants Commission, Council for Scientific and Industrial Research, Government of India. The authors would like to thank Mr. Bharat Pareek for his technical assistance and entire lab management during the manuscript preparation. We apologize to various authors whose work could not be included due to space limitations.

Conflict of interest: The authors do not have any actual or potential conflicts of interests to disclose.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Vibhuti Joshi
    • 1
  • Arun Upadhyay
    • 1
  • Ayeman Amanullah
    • 1
  • Ribhav Mishra
    • 1
  • Amit Mishra
    • 1
    Email author
  1. 1.Cellular and Molecular Neurobiology UnitIndian Institute of Technology JodhpurJodhpurIndia

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