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암 치료 표적으로써 prostate apoptosis response-4(Par-4)

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Author(s)
Seon Min WooTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
생명과학회지
Issued Date
2015
Volume
25
Issue
8
Keyword
ApoptosisCancerProstate apoptosis response-4 (Par-4)Nuclear factor-κB (NF-κB)Selective for apoptosis in cancer cell (SAC) domain
Abstract
Prostate apoptosis response-4 (Par-4) was originally identified in androgen-independent prostate cancer
cells undergoing apoptosis. Par-4 is ubiquitously expressed in normal cells and tissues, but it is
downregulated in several types of cancers. Par-4 is a 38 kDa tumor suppressor protein encoded by
the PARW gene. Par-4 promotes apoptosis in a variety of cancerous cells, but not in normal cells. In
this review, we focused on the structure, expression and function of Par-4 in apoptotic signaling
pathway. Functional domains of Par-4 include two nuclear localization sequences (NLS), a leucine zipper
(LZ) domain, a nuclear export sequence (NES) and selective for apoptosis in cancer cell (SAC)
domain. Many studies have underlined the importance of Par-4 in preventing cancer development.
The activity of Par-4 is differently regulated by localization of intracellular and extracellular Par-4.
Intracellular Par-4 inhibits Akt- and NF-κB-mediated cell survival pathways and downregulates Bcl-2
expression. Extracellular Par-4 activates the extrinsic apoptotic pathway by binding to cell surface receptor
GRP78, a stress response protein that is in the endoplasmic reticulum (ER). Endogenous Par-4
sensitizes cancer cells to various apoptotic stimuli, while exogenous Par-4 enhances SAC domain-dependent
apoptosis in cancer cells, but not normal cells. Therefore, Par-4 is an attractive target for cancer
therapy.
Par-4는 종양 억제 유전자로 암세포 선택적으로 세포사멸을 증진하는 기능을 가진다. Par-4 유전자는 nuclear
localization sequences (NLS), leucine zipper (LZ), nuclear export sequence (NES), selective for apoptosis in cancer
cells (SAC)의 네 가지 도메인을 가지고 있다. 이 중에서도 SAC 도메인이 Par-4에 의한 세포사멸에 중요한
역할을 하며, 이러한 Par-4의 활성화는 세포 내 경로와 세포 외 경로로 나누어진다. 세포질 내의 Par-4는 핵 내로
이동하여 NF-κB 매개의 세포 성장 경로를 억제하고 세포 밖으로 분비된 Par-4는 세포 표면에 존재하는 수용체인
GRP78과 결합하여 세포 사멸을 유도한다. 따라서 Par-4의 발현을 증가시키는 물질에 의한 세포 사멸뿐만 아니라
암세포에서 발현이 낮은 Par-4의 과발현을 통하여 세포사멸 민감화가 증진된다. 따라서 Par-4는 암 치료의 강력한
표적으로의 가능성을 가지고 있다.
Alternative Title
Prostate Apoptosis Response-4 (Par-4) as a Cancer Therapeutic Target
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Seon Min Woo and Taeg Kyu Kwon. (2015). 암 치료 표적으로써 prostate apoptosis response-4(Par-4). 생명과학회지, 25(8), 947–952. doi: 10.5352/JLS.2015.25.8.947
Type
Article
ISSN
1225-9918
DOI
10.5352/JLS.2015.25.8.947
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33109
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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