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. 2006 Mar 1;11(1):109. doi: 10.2478/s11658-006-0011-9

Degradation and beyond: Control of androgen receptor activity by the proteasome system

Tomasz Jaworski 1,✉
PMCID: PMC6275697  PMID: 16847754

Abstract

The androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors which mediates the action of androgens in the development of urogenital structures. AR expression is regulated post-translationally by the ubiquitin/proteasome system. This regulation involves more complex mechanisms than typical degradation. The ubiquitin/proteasome system may regulate AR via mechanisms that do not engage in receptor turnover. Given the critical role of AR in sexual development, this complex regulation is especially important. Deregulation of AR signalling may be a causal factor in prostate cancer development. AR is the main target in prostate cancer therapies. Due to the critical role of the ubiquitin/proteasome system in AR regulation, current research suggests that targeting AR degradation is a promising approach.

Key words: AR, Degradation, Prostate cancer, Proteasome, Transcription, Ubiquitin

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Abbreviations used

AATF

apoptosis antagonizing factor

APIS complex

AAA proteins independent of 20S

ARA54

AR-associated protein 54

ARA70

AR-associated protein 70

ARE

androgen responsive element

ARNIP

AR N-terminal interacting protein

bFGF

basic fibroblast growth factor

CARM1

coactivator-associated arginine methyltransferase 1

CHIP

C-terminus Hsp70 interacting protein

DBD

DNA binding domain

E6-AP

E6-associated protein

GRIP-1

glucocorticoid receptor interacting protein 1

GSK3β

glycogen synthase kinase 3β

HDAC1

histone deacetylase 1

HECT

homologous to the E6-AP C-terminus

HEK293

human embryonal kidney cell line

HepG2

human hepatoma cell line

Hsp90

heat shock protein 90

IGF-1

insulin-like growth factor 1

IL-6

interleukin 6

KLK2

kallikrein 2

KLKK

lysine (K), leucine (L)

LBD

ligand binding domain

LNCaP

lymph node carcinoma of prostate cell line

MAPK

mitogen activated protein kinase

Mdm2

Murine double minute 2

NcoR

nuclear receptor corepressor

NEDD8

neural precursor cell-expressed developmentally down-regulated

NLS

nuclear localisation signal

p/CAF

p300/CBP-associated factor

p300/CBP

CREB-binding protein

PC3

human prostate carcinoma cell line

PEST

proline (P), glutamic acid (E), serine (S), threonine (T)

PI3K

phosphoinositide-3 kinase

PIAS1

protein inhibitor of activated STAT

PKA

protein kinase A

PKC

protein kinase C

PR

progesterone receptor

PRMT1

protein arginine methyltransferase 1

PROTAC

proteolysis targeting chimeric molecule

PSA

prostate specific antigen

PSMA7

proteasome alpha subunit 7

P-TEFb

positive transcription elongation factor b

PTEN

phosphatase and tensin homolog deleted on chromosome 10

RING

really interesting new gene

RNA Pol II

RNA polymerase II

SCF ligase

Skp2/cullin1/F-box

SMRT

silencing mediator of retinoic acid and thyroid hormone receptor

SNURF

small nuclear RING finger

SRC1

steroid receptor coactivator 1

Sugl

suppressor of Gal

SUMO

small ubiquitin-like modifier

SWI/SNF

mating type switching/sucrose non-fermenting

TBL1

transducin-β-like

TBLR1

transduction-β-like-related protein

TBP

TATA binding protein

TFIIB, D, F, H

general transcription factors

TRAP

thyroid hormone receptor-associated protein

TSG101

tumour susceptibility gene 101

UAC

ubiquitin activating enzyme

UBC

ubiquitin conjugating enzyme

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