Prenylated Rab acceptor RABAC1 inhibits anti-apoptotic protein BCL2A1 and induces apoptosis

被引：10

作者：

Kim, Jong-Tae ^{[1
]}

Cho, Hee Jun ^{[1
]}

Cho, Mi-Young ^{[2
]}

Lim, Jeewon ^{[1
,3
]}

Park, Eun Sun ^{[1
,3
]}

Lim, Jong-Seok ^{[4
,5
]}

Lee, Hee Gu ^{[1
,3
]}

机构：

[1] Korea Res Inst Biosci & Biotechnol, Immunotherapy Res Ctr, Daejeon, South Korea

[2] SKKU Adv Inst Nanotechnol, Suwon, South Korea

[3] Univ Sci & Technol, Dept Biomol Sci, Daejeon, South Korea

[4] Sookmyung Womens Univ, Dept Biomol Sci, Seoul, South Korea

[5] Sookmyung Womens Univ, Cellular Heterogene Res Ctr, Seoul, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2019年 / 513卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

RABAC1; PRA; BCL2A1; BCL2; Apoptosis; UP-REGULATION; POTENTIAL MECHANISM; FAMILY PROTEINS; BCL-2; EXPRESSION; CANCER; BFL-1; CHEMORESISTANCE; GTPASES; DISSOCIATION;

D O I：

10.1016/j.bbrc.2019.04.080

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The B cell lymphoma 2 (BCL2) family of proteins constitutes a critical intracellular checkpoint in the intrinsic apoptosis pathway. Among BCL2 members, the anti-apoptotic protein BCL2A1 mediates the resistance to BCL2 inhibitors and may be considered as a target for anti-cancer therapy. Here, we report that prenylated Rab acceptor 1 (RABAC1 or PRA1) inhibits the anti-apoptotic activity of BCL2A1 and induces apoptosis in AGS gastric cancer cells. Protein interaction of BCL2A1 and RABAC1 was verified by an in-vitro glutathione-S-transferase pull-down assay, immunoprecipitation, and confocal microscopy. When apoptosis was induced by cisplatin, the anti-apoptotic activity of BCL2A1 was blocked by RABAC1 expression. RABAC1 caused caspase-3 activation and decreased cell proliferation, clonogenic cell survival, and cell migration and invasion. We suggest RABAC1 as a potential therapeutic target for BCL2A1-related cancer. (C) 2019 Published by Elsevier Inc.

引用

页码：940 / 946

页数：7

共 36 条

[21] JWA is required for the antiproliferative and pro-apoptotic effects of all-trans retinoic acid in HeLa cells
Mao, Wen-Ge
Liu, Zu-Long
Chen, Rui
Li, Ai-Ping
Zhou, Jian-Wei
[J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2006, 33 (09): : 816 - 824
[22] High expression of bfl-1 contributes to the apoptosis resistant phenotype in B-cell chronic lymphocytic leukemia
Morales, AA
Olsson, A
Celsing, F
Österborg, A
Jondal, M
Osorio, LM
[J]. INTERNATIONAL JOURNAL OF CANCER, 2005, 113 (05) : 730 - 737
[23] Abnormal expression of apoptosis-related genes in haematological malignancies:: overexpression of MYC is poor prognostic sign in mantle cell lymphoma
Nagy, B
Lundán, T
Larramendy, ML
Aalto, Y
Zhu, Y
Niini, T
Edgren, H
Ferrer, A
Vilpo, J
Elonen, E
Vettenranta, K
Franssila, K
Knuutila, S
[J]. BRITISH JOURNAL OF HAEMATOLOGY, 2003, 120 (03) : 434 - 441
[24] Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia
Olsson, A.
Norberg, M.
Okvist, A.
Derkow, K.
Choudhury, A.
Tobin, G.
Celsing, F.
Osterborg, A.
Rosenquist, R.
Jondal, M.
Osorio, L. M.
[J]. BRITISH JOURNAL OF CANCER, 2007, 97 (06) : 769 - 777
[25] Park IC, 1997, ANTICANCER RES, V17, P4619
[26] Rab GTPases, intracellular traffic and disease
Seabra, MC
Mules, EH
Hume, AN
[J]. TRENDS IN MOLECULAR MEDICINE, 2002, 8 (01) : 23 - 30
[27] Bfl-1/A1 functions, similar to Mcl-1, as a selective tBid and Bak antagonist
Simmons, M. J.
Fan, G.
Zong, W-X
Degenhardt, K.
White, E.
Gelinas, C.
[J]. ONCOGENE, 2008, 27 (10) : 1421 - 1428
[28] Yip3 catalyses the dissociation of endosomal Rab-GDI complexes
Sivars, U
Aivazian, D
Pfeffer, SR
[J]. NATURE, 2003, 425 (6960) : 856 - 859
[29] Praf2 Is a Novel Bcl-xL/Bcl-2 Interacting Protein with the Ability to Modulate Survival of Cancer Cells
Vento, Maria Teresa
Zazzu, Valeria
Loffreda, Alessia
Cross, Justin R.
Downward, Julian
Stoppelli, Maria Patrizia
Iaccarino, Ingram
[J]. PLOS ONE, 2010, 5 (12):
[30] BCL2A1: the underdog in the BCL2 family
Vogler, M.
[J]. CELL DEATH AND DIFFERENTIATION, 2012, 19 (01) : 67 - 74

← 1 2 3 4 →