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Novel Ubiquitin E3 Ligases as Targets for Cancer Therapy: Focus on Breast Cancer-Associated Gene 2 (BCA2)

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Resistance to Proteasome Inhibitors in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT))

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Abstract

The struggle to find new cancer targets continues unabated. With this in mind, E3 ligases (also called E3 ubiquitin ligases) constitute a large and diverse family of genes that play a role in the ubiquitination of proteins as well as in a myriad of other important activities in cells including, but not limited to, DNA repair and proliferation. Breast cancer-associated protein 2 (BCA2) is an E3 ligase that is expressed in a large number of invasive breast cancers and is involved in several important cellular functions. In this chapter we describe the mechanisms that control the expression and half-life of BCA2 and the association between high expression of BCA2 and breast cancer tumor grade. Furthermore, we explore the role that this E3 ligase may play in cancer progression. Finally, we examine the potential effects of E3 ligases, including BCA2, a novel class of wide-ranging therapeutic cancer targets.

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Abbreviations

ALDH:

Aldehyde dehydrogenase

APC:

Anaphase-promoting complex

BARD1:

BRCA1-associated RING domain 1

BCA2:

Breast cancer-associated gene 2

BER:

Base excision repair

BZF:

BCA2 zinc-finger

C-CBL:

Casitas B-lineage lymphoma

Cdc4:

Cell division cycle 4

CDK:

Cyclin-dependent kinase

CGH:

Comparative genomic hybridization

CHX:

Cycloheximide

DUBs:

Deubiquitinating enzymes

E1:

Ubiquitin-activating enzyme

E2s:

Ubiquitin-conjugating enzymes

E3s:

Ubiquitin ligases

E6-AP:

E6-associated protein

EFP:

Estrogen-responsive finger protein

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

FBW7:

F-box and WD repeat domain-containing 7

FR:

Folate receptor

HER2:

Epidermal growth factor receptor 2

hHR23a:

Human homolog of Rad23 variant A

HOS:

Homolog of Slimb

HPV:

Human papillomavirus

HSV-1:

Herpes simplex virus-1

K:

Lysine

LMP-1:

Latent membrane protein 1

MetAP-2:

Methionine aminopeptidase-2

NER:

Nucleotide excision repair

PDGFRα:

Platelet-derived growth factor receptor alpha

PR:

Progesterone receptor

Protac:

Proteolysis targeting chimeric molecule

RNAi:

RNA interference

RTK:

Receptor tyrosine kinases

SCF:

Skp-Cullin-F-box

TOR:

Target of rapamycin

UBL:

Ubiquitin-like

UPS:

Ubiquitin-proteasome system

VHL:

von Hippel-Lindau

XP:

Xeroderma pigmentosum

XPC:

XP group C protein

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Authors and Affiliations

  1. Next Generation Sequencing Lab, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5

    Yutaka Amemiya M.Sc., Ph.D.

  2. Biological Sciences Platform, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5

    Stephanie Bacopulos & Arun Seth Ph.D.

  3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Arun Seth Ph.D.

Authors
  1. Yutaka Amemiya M.Sc., Ph.D.
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  2. Stephanie Bacopulos
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  3. Arun Seth Ph.D.
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Correspondence to Arun Seth Ph.D. .

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  1. Wayne State University, Detroit, Michigan, USA

    Q. Ping Dou

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Amemiya, Y., Bacopulos, S., Seth, A. (2014). Novel Ubiquitin E3 Ligases as Targets for Cancer Therapy: Focus on Breast Cancer-Associated Gene 2 (BCA2). In: Dou, Q. (eds) Resistance to Proteasome Inhibitors in Cancer. Resistance to Targeted Anti-Cancer Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-06752-0_13

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