PMID- 33125132
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20210920
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 44
IP  - 6
DP  - 2020 Dec
TI  - VDAC upregulation and alphaTAT1‑mediated alpha‑tubulin acetylation contribute to 
      tanespimycin‑induced apoptosis in Calu‑1 cells.
PG  - 2725-2734
LID - 10.3892/or.2020.7789 [doi]
AB  - Voltage‑dependent anion channel 1 (VDAC1) functions as a porin in the 
      mitochondrial outer membrane (MOM) and plays important roles in 
      mitochondria‑mediated cell apoptosis. VDAC1 interacts with a variety of proteins, 
      such as Bcl‑2 family proteins, hexose kinase (HK), adenine nucleotide translocase 
      (ANT) and alpha‑tubulin. However, the association between VDAC1 and alpha‑tubulin, 
      particularly between VDAC1 and acetylated alpha‑tubulin (Ac‑alpha‑tubulin), in apoptosis 
      remains unclear. The present study revealed that the heat shock protein 90 
      inhibitor, tanespimycin, induced VDAC1 upregulation and alpha‑tubulin acetylation 
      during Calu‑1 cell apoptosis in human lung cancer. Hsp90 mediated the expression 
      level of VDAC1, and the acetylation of alpha‑tubulin was enhanced in an alpha‑tubulin 
      acetyltransferase 1 (alphaTAT1)‑dependent manner following an increase in VDAC1 
      expression. Docetaxel, as an inhibitor of microtubules, augmented the expression 
      of Ac‑alpha‑tubulin, VDAC1 and Bax induced by tanespimycin and increased the degree 
      of caspase activation. Immunoprecipitation (IP) experiments revealed that 
      Ac‑alpha‑tubulin, alpha‑tubulin and VDAC1 were co‑precipitated in the IP complex, in 
      which alpha‑tubulin expression was decreased and VDAC1 proteins were oligomerized, 
      and that the p‑AKT/glycogen synthase kinase 3beta (GSK3beta) signalling pathway 
      mediated the opening of VDAC1. Therefore, it can be asserted that the acetylation 
      of alpha‑tubulin and VDAC1 upregulation or oligomerization induced by tanespimycin 
      may lead to mitochondrial permeability and consequently induce the apoptosis of 
      lung cancer cells. These findings provide evidence for the use of a combination 
      of drugs that target VDAC1 and tubulin to induce tumour cell apoptosis.
FAU - Wang, Qilin
AU  - Wang Q
AD  - School of Life Sciences, Liaocheng University, Liaocheng, Shandong 252059, 
      P.R. China.
FAU - Liu, Xiangguo
AU  - Liu X
AD  - School of Life Sciences, Shandong University, Qingdao, Shandong 266237, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20201005
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Benzoquinones)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Microtubule Proteins)
RN  - 0 (Tubulin)
RN  - 0 (VDAC1 protein, human)
RN  - 15H5577CQD (Docetaxel)
RN  - 4GY0AVT3L4 (tanespimycin)
RN  - EC 1.6.- (Voltage-Dependent Anion Channel 1)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.108 (ATAT1 protein, human)
SB  - IM
MH  - Acetylation/drug effects
MH  - Acetyltransferases/*metabolism
MH  - Apoptosis/drug effects
MH  - Benzoquinones/*pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Docetaxel/pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - HSP90 Heat-Shock Proteins/antagonists & inhibitors/metabolism
MH  - Humans
MH  - Lactams, Macrocyclic/*pharmacology/therapeutic use
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Microtubule Proteins/*metabolism
MH  - Mitochondrial Membranes/drug effects/metabolism
MH  - Permeability/drug effects
MH  - Protein Multimerization/drug effects
MH  - Tubulin/metabolism
MH  - Up-Regulation/drug effects
MH  - Voltage-Dependent Anion Channel 1/*genetics
OTO - NOTNLM
OT  - VDAC1
OT  - alpha-tubulin acetylation
OT  - Hsp90
OT  - alphaTAT1
OT  - tanespimycin
OT  - apoptosis
EDAT- 2020/10/31 06:00
MHDA- 2021/08/03 06:00
CRDT- 2020/10/30 12:10
PHST- 2020/02/09 00:00 [received]
PHST- 2020/09/09 00:00 [accepted]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/10/30 12:10 [entrez]
AID - 10.3892/or.2020.7789 [doi]
PST - ppublish
SO  - Oncol Rep. 2020 Dec;44(6):2725-2734. doi: 10.3892/or.2020.7789. Epub 2020 Oct 5.