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Nuclear Subdomains and Cancer

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Book cover Advances in Nuclear Architecture

Abstract

Cancer develops when genetic changes, such as the activation of oncogenes and inactivation of tumour suppressors, allow a cell to escape the normal growth and proliferation restrictions. These functional changes ultimately result in structural alterations at both the nuclear and cellular levels. As such, cell morphology and biological marker expression are some of the main criteria in tumour pathology for diagnosis and prognosis. The development of advanced microscopy techniques has provided a much more detailed map of the nuclear landscape, and because of this, structural changes in subnuclear bodies induced during oncogenesis can be readily visualized. This type of analysis has identified novel cancer biomarkers in the form of nuclear structures associated with malignancy, such as the perinucleolar compartment (PNC). It has also allowed a much more detailed examination of nuclear body function, which has provided novel mechanisms and regulators of tumour suppression and oncogenesis. This chapter will focus on three of the most important subnuclear domains for cancer biology: promyelocytic leukemia nuclear bodies (PML NBs), the nucleolus, and the perinucleolar compartment (PNC).

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Abbreviations

AgNORs:

Silver stained nucleolar organizer regions

AKT:

V-akt murine thymoma viral oncogene homolog 1

ALT:

Alternative lengthening of telomeres

APL:

Acute promyelocytic leukaemia

ARF:

Alternate reading frame protein

ASK1:

Mitogen-activated protein kinase kinase kinase 5

ATM:

Ataxia telangiectasia mutated

ATR:

ATM- and Rad3-related

ATRIP:

ATR-interacting protein

Bcl-2:

B-cell CLL/lymphoma 2

BCL2L11:

Bim/BCL2-like 11

Bop1:

Block of proliferation 1

BLM:

Bloom syndrome protein

Brca1:

Breast cancer 1

Br-U:

Bromouridine

CASP8AP2:

Caspase 8 associated protein 2

CBP:

CREB binding protein

CDK:

Cyclin-dependent kinase

CK1:

Casein kinase 1

CKII:

Casein kinase 2

CUG-BP:

CUG triplet repeat, RNA binding protein 1

DAXX:

Death-domain associated protein

DBA:

Diamond-Blackfan anemia

DC:

Dyskeratosis congenital

DKC1:

Dyskeratosis congenital, dyskerin

DFC:

Dense fribrillar component

E6AP:

E6-associated protein

ERK2:

Extracellular-signal-regulated protein kinase 2

FADD:

Fas (TNFRSF6)-associated via death domain

FCs:

Fibrillar centres

FLASH:

Flice-associated huge protein

FOXO:

Forkhead box

γ-H2A.X:

Phosphorylated H2A.X

GC:

Granular component

HAUSP:

Herpes-associated ubiquitin-specific protease

HDAC1:

Histone deacetylase 1

HIC1:

Hypermethylated in cancer 1

HIPK2:

Homeodomain interacting protein kinase 2

hMSH6:

Human mutS homolog 2

HP1:

Heterochromatin protein 1

HPV:

Human papilloma virus

HSV1:

Herpes Simplex Virus 1

IAPs:

Inhibitor of apoptosis proteins

IFNs:

Interferons

IGF-1:

Insulin-like growth factor 1

IκB:

Inhibitor of NF-κB

ING-1:

Inhibitor of growth 1

IRES:

Internal ribosome entry site

IRS:

Insulin receptor substrate

JNK:

c-Jun-N-terminal kinase

Kap1:

KRAB domain-associated protein 1

KSRP:

KH-type splicing regulatory protein

KSHV:

Karposi sarcoma-associated herpesvirus

LANA2:

Latency associated nuclear antigen 2

MAPK:

Mitogen-activated protein kinase

MDM2:

Mouse double minute 2

Mina53:

MYC induced nuclear antigen

Misu:

Myc-induced SUN domain-containing protein

Mre11:

Meiotic recombination 11

MRN:

Mre11, Rad50, NBS1

mRNA:

Messenger RNA

MTA2:

Metastasis-associated protein 2

mTOR:

Mammalian target of rapamycin

NBS1:

Nijmegen breakage syndrome 1

Nop2:

Nucleolar protein homolog (yeast) 2

NORs:

Nucleolar organizer regions

NPM:

Nucleophosmin

NF-κB:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

OPT:

Oct1, PTF transcription

PAWR:

PRKC, apoptosis, WT1, regulator

PI3K:

Phosphatidylinositol 3-kinase

PODs:

PML oncogenic domains

PML NBs:

Promyelocytic leukemia nuclear bodies

PNC:

Perinucleolar compartment

PP2A:

Protein phosphatase 2

pRB:

Retinoblastoma protein

pol:

Polymerase

PRMT1:

Protein arginine methyltransferase 1

PTEN:

Phosphatase and tensin homolog

PTB:

Polypyrimidine track binding protein

PTF:

PSE-binding factor subunit delta,small nuclear RNA activating complex, polypeptide 2, 45kDa

RanBP2:

Ran Binding Protein 2

RARα:

Retinoic acid receptor alpha

RBCC:

RING zinc finger, two B-boxes and coiled-coil domain

rDNA:

Ribosomal DNA

RecQL4:

RecQ protein-like 4

RING:

Really interesting new gene

RMRP:

RNA component of mitochondrial RNA processing endoribonuclease

RNF4:

Ring finger protein 4

RPLs:

Ribosomal proteins of the large subunit

RPSs:

Ribosomal proteins of the small subunit

rRNA:

Ribosomal RNA

RSK:

Ribosomal protein S6 kinase, RPS6KA1

SAHF:

Senescence-induced heterochromatin foci

scaRNA:

Small Cajal body RNA

SCE:

Sister-chromatid exchange

SENPs:

SUMO1/sentrin specific peptidase 1

SFCs:

Splicing factor compartments

SIM:

SUMO-interacting motif

SIRT1:

Sirtuin (silent mating type information regulation 2 homolog) 1

snRNPs:

Small nuclear ribonucleoproteins

SRP:

Signal recognition particle

SUMO:

Small ubiquitin modifier

TAF1:

TBP-associated factor 1

TCAB1:

Telomerase Cajal body protein 1

TERC:

Telomerase RNA component

TERT:

Telomerase reverse transcriptase

TGF-β:

Transforming growth factor beta

THAP1:

THAP domain containing apoptosisassociated protein 1

TIF-IA:

Transcription initiation factor IA

TIF-IB:

Transcription initiation factor IB

TIP60:

HIV-1 Tat interactive protein, KAT5 K(lysine) acetyltransferase 5

TNFα:

Tumour necrosis factor alpha

TNFSF10:

TRAIL/TNF superfamily, member 10

TopBP1:

Topoisomerase (DNA) II binding protein 1

TRF2:

Telomere repeat binding factor 2

TSA:

Trichostatin A

TTF-1:

Transcription terminator factor-1

SL1:

Promoter selectivity factor

UBC9:

Ubiquitin-conjugating enzyme E2I(UBC9 homolog, yeast)

UBF:

Upstream binding factor

USP7:

Ubiquitin specific protease 7

WRN:

Werner syndrome, RecQ helicase-like

YAP:

Yes-associated protein

ZIPK:

ZIP kinase, death-associated protein kinase 3

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Acknowledgements

G.D. is the Cameron Scientist in Cancer Biology of the Dalhousie Cancer Research Program and a Canadian Institutes of Health Research (CIHR) New Investigator. This work is funded in part by operating grants from Nova Scotia Health Research Foundation (NSHRF) (2007–3348) and the CIHR (MOP-84260). K.L.C. is supported by postdoctoral fellowships from the NSHRF and the Killam Trusts. We would also like to apologize to those colleagues whom we could only cite indirectly in this review.

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Authors and Affiliations

  1. Department of Pathology, Dalhousie University, Rm 11G1, Sir Charles Tupper Medical Building, 5859 University Avenue, NS, B3H 4 H7, Halifax, Canada

    Kendra L. Cann & Graham Dellaire

  2. Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada

    Kendra L. Cann & Graham Dellaire

  3. Feinberg School of Medicine, Cell and Molecular Biology, Northwestern University, Chicago, Illinois, 60611, USA

    Sui Huang

Authors
  1. Kendra L. Cann
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  2. Sui Huang
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  3. Graham Dellaire
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Corresponding author

Correspondence to Graham Dellaire .

Editor information

Editors and Affiliations

  1. Department of Mathematics, Imperial College, Queen's Gate 180, London, SW7 2AZ, United Kingdom

    Niall M. Adams

  2. Div. Molecular Biosciences, Imperial College London, London, SW7 2AZ, United Kingdom

    Paul S. Freemont

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© 2011 Springer Netherlands

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Cann, K.L., Huang, S., Dellaire, G. (2011). Nuclear Subdomains and Cancer. In: Adams, N., Freemont, P. (eds) Advances in Nuclear Architecture. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9899-3_1

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