Bax-/- bak-/- cells exhibit p27 Thr198 phosphorylation and autophagy

被引：6

作者：

Cui, Qinghua

Valentin, Mayda ^{[2
]}

Janumyan, Yelena ^{[2
]}

Yang, Elizabeth ^{[1
,2
,3
,4
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA

[2] Dept Canc Biol, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA

[4] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

来源：

AUTOPHAGY | 2009年 / 5卷 / 02期

关键词：

Bax; Bak; Bcl-x(L); autophagy; G(0) arrest; p27; phosphorylation; CYCLE ENTRY; G(0) FUNCTION; P27(KIP1); APOPTOSIS; BCL-X(L); BCL-2; INHIBITION; PROTEINS; KINASES; CANCER;

D O I：

10.4161/auto.5.2.7618

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Cell cycle arrest in Go and autophagy share features in common. The Bcl-2 family exerts cell cycle effects in addition to regulating apoptosis. Bcl-2 and Bcl-x(L) upregulate p27 and promote Go arrest. Recently, we asked whether autophagy was involved in BcI-2 and Bcl-x(L)-mediated cell cycle arrest, and found that autophagy was activated, but not required, for Go arrest. We also discovered that the cell cycle function of Bcl-2 and Bcl-x(L) was dependent on Bax and Bak, and in bax(-/-) bak(-/-) double knockout cells, features of Go quiesecence were already present and p27 was constitutively elevated. Here, we queried the presence of autophagy in bax(-/-) bak(-/) double knockout cells, and report the phosphorylation of p27 at Thr198, which is known to occur in autophagy, as well as constitutive Atg5 induction and LC3-I to -II conversion. These findings in bax(-/-) bak(-/) cells suggest that a physiological role of Bax and Bak may be the suppression of autophagy.

引用

收藏

页码：263 / 264

页数：2

相关论文

共 16 条

[1]

Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization [J].

Fujita, N ;

Sato, S ;

Tsuruo, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (49) :49254-49260

[2]

BCL-xL and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases [J].

Greider, C ;

Chattopadhyay, A ;

Parkhurst, C ;

Yang, E .

ONCOGENE, 2002, 21 (51) :7765-7775

[3]

Hosokawa N, 2007, FEBS LETT, V581, P2623, DOI 10.1016/j.febslet.2006.04.008

[4]

G0 Function of BCL2 and BCL-xL Requires BAX, BAK, and p27 Phosphorylation by Mirk, Revealing a Novel Role of BAX and BAK in Quiescence Regulation [J].

Janumyan, Yelena ;

Cui, Qinghua ;

Yan, Ling ;

Sansam, Courtney G. ;

Valentin, Mayda ;

Yang, Elizabeth .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (49) :34108-34120

[5]

Bcl-xL/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry [J].

Janumyan, YM ;

Sansam, CG ;

Chattopadhyay, A ;

Cheng, NL ;

Soucie, EL ;

Penn, LZ ;

Andrews, D ;

Knudson, CM ;

Yang, E .

EMBO JOURNAL, 2003, 22 (20) :5459-5470

[6]

Autophagy for cancer therapy through inhibition of pro-apoptotic proteins and mammalian target of rapamycin signaling [J].

Kim, Kwang Woon ;

Mutter, Robert W. ;

Cao, Carolyn ;

Albert, Jeffrey M. ;

Freeman, Michael ;

Hallahan, Dennis E. ;

Lu, Bo .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (48) :36883-36890

[7]

Antitumour effect of cyclin-dependent kinase inhibitors (p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIPI on malignant glioma cells [J].

Komata, T ;

Kanzawa, T ;

Takeuchi, H ;

Germano, IM ;

Schreiber, M ;

Kondo, Y ;

Kondo, S .

BRITISH JOURNAL OF CANCER, 2003, 88 (08) :1277-1280

[8]

The energy sensing LKB1-AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis [J].

Liang, Jiyong ;

Shao, Shan H. ;

Xu, Zhi-Xiang ;

Hennessy, Bryan ;

Ding, Zhiyong ;

Larrea, Michelle ;

Kondo, Seiji ;

Dumont, Dan J. ;

Gutterman, Jordan U. ;

Walker, Cheryl L. ;

Slingerland, Joyce M. ;

Mills, Gordon B. .

NATURE CELL BIOLOGY, 2007, 9 (02) :218-U125

[9]

Growth factor regulation of autophagy and cell survival in the absence of apoptosis [J].

Lum, JJ ;

Bauer, DE ;

Kong, M ;

Harris, MH ;

Li, C ;

Lindsten, T ;

Thompson, CB .

CELL, 2005, 120 (02) :237-248

[10]

Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells [J].

Mizushima, N ;

Yamamoto, A ;

Hatano, M ;

Kobayashi, Y ;

Kabeya, Y ;

Suzuki, K ;

Tokuhisa, T ;

Ohsumi, Y ;

Yoshimori, T .

JOURNAL OF CELL BIOLOGY, 2001, 152 (04) :657-667