Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Transmembrane Protein 166 and its Significance

Author(s): Yanwei Yang, Lingxue Zhou, Fushan Xue, Lixin An, Mu Jin and Li Li*

Volume 28, Issue 4, 2021

Published on: 02 October, 2020

Page: [382 - 387] Pages: 6

DOI: 10.2174/0929866527666201002150316

Price: $65

Abstract

Transmembrane protein 166 (TMEM166) is a lysosomal/endoplasmic reticulum (ER)-associated protein found in different species where it functions as a regulator of programmed cell death through autophagy and apoptosis. It is expressed in a variety of normal tissues and organs, and it is involved in a wide variety of physiological and pathological processes, including cancers, infection, autoimmune diseases, and neurodegenerative diseases. Previous studies indicated that TMEM166 is associated with autophagosomal membrane development. TMEM166 can cause lysosomal membrane permeabilization (LMP) leading to the release of proteolytic enzymes, e.g., cathepsins, that may cause potential mitochondrial membrane damage, which triggers several autophagic and apoptotic events. A low level of TMEM166 expression is also found in tumors, while high level of TMEM166 is found in brain ischemia. In addition, loss of TMEM166 leads to impaired NSC self-renewal and differentiation along with a decrease in autophagy. These findings offer a comprehensive understanding of the pathways involved in the role of TMEM166 in programmed cell death and treatment of various diseases.

Keywords: TMEM166, autophagy, apoptosis, tumor, cerebral ischemia, embryonic neurogenesis.

« Previous Next »
Graphical Abstract

[1]
Sun, W.; Ma, X.M.; Bai, J.P.; Zhang, G.Q.; Zhu, Y.J.; Ma, H.M.; Guo, H.; Chen, Y.Y.; Ding, J.B. Transmembrane protein 166 expression in esophageal squamous cell carcinoma in Xinjiang, China. Asian Pac. J. Cancer Prev., 2012, 13(8), 3713-3716.
[http://dx.doi.org/10.7314/APJCP.2012.13.8.3713] [PMID: 23098460]
[2]
Hu, J.; Li, G.; Qu, L.; Li, N.; Liu, W.; Xia, D.; Hongdu, B.; Lin, X.; Xu, C.; Lou, Y.; He, Q.; Ma, D.; Chen, Y. TMEM166/EVA1A interacts with ATG16L1 and induces autophagosome formation and cell death. Cell Death Dis., 2016, 7(8), e2323.
[http://dx.doi.org/10.1038/cddis.2016.230] [PMID: 27490928]
[3]
Xu, D.; Yang, F.; He, H.; Hu, J.; Lv, X.; Ma, D.; Chen, Y.Y. Expression of TMEM166 protein in human normal and tumor tissues. Appl. Immunohistochem. Mol. Morphol., 2013, 21(6), 543-552.
[http://dx.doi.org/10.1097/PAI.0b013e31824e93d1] [PMID: 22495369]
[4]
Xie, H.; Hu, J.; Pan, H.; Lou, Y.; Lv, P.; Chen, Y. Adenovirus vector-mediated FAM176A overexpression induces cell death in human H1299 non-small cell lung cancer cells. BMB Rep., 2014, 47(2), 104-109.
[http://dx.doi.org/10.5483/BMBRep.2014.47.2.090] [PMID: 24257118]
[5]
Chang, Y.; Li, Y.; Hu, J.; Guo, J.; Xu, D.; Xie, H.; Lv, X.; Shi, T.; Chen, Y. Adenovirus vector-mediated expression of TMEM166 inhibits human cancer cell growth by autophagy and apoptosis in vitro and in vivo. Cancer Lett., 2013, 328(1), 126-134.
[http://dx.doi.org/10.1016/j.canlet.2012.08.032] [PMID: 22960574]
[6]
Wang, L.; Yu, C.; Lu, Y.; He, P.; Guo, J.; Zhang, C.; Song, Q.; Ma, D.; Shi, T.; Chen, Y. TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis. Apoptosis, 2007, 12(8), 1489-1502.
[http://dx.doi.org/10.1007/s10495-007-0073-9] [PMID: 17492404]
[7]
Yang, Z.; Klionsky, D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol., 2010, 22(2), 124-131.
[http://dx.doi.org/10.1016/j.ceb.2009.11.014] [PMID: 20034776]
[8]
Maycotte, P.; Thorburn, A. Autophagy and cancer therapy. Cancer Biol. Ther., 2011, 11(2), 127-137.
[http://dx.doi.org/10.4161/cbt.11.2.14627] [PMID: 21178393]
[9]
Mizushima, N.; Levine, B. Autophagy in mammalian development and differentiation. Nat. Cell Biol., 2010, 12(9), 823-830.
[http://dx.doi.org/10.1038/ncb0910-823] [PMID: 20811354]
[10]
Rabinowitz, J.D.; White, E. Autophagy and metabolism. Science, 2010, 330(6009), 1344-1348.
[http://dx.doi.org/10.1126/science.1193497] [PMID: 21127245]
[11]
Ravikumar, B.; Sarkar, S.; Davies, J.E.; Futter, M.; Garcia-Arencibia, M.; Green-Thompson, Z.W.; Jimenez-Sanchez, M.; Korolchuk, V.I.; Lichtenberg, M.; Luo, S.; Massey, D.C.; Menzies, F.M.; Moreau, K.; Narayanan, U.; Renna, M.; Siddiqi, F.H.; Underwood, B.R.; Winslow, A.R.; Rubinsztein, D.C. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev., 2010, 90(4), 1383-1435.
[http://dx.doi.org/10.1152/physrev.00030.2009] [PMID: 20959619]
[12]
Mathew, R.; White, E. Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr. Opin. Genet. Dev., 2011, 21(1), 113-119.
[http://dx.doi.org/10.1016/j.gde.2010.12.008] [PMID: 21255998]
[13]
Banerjee, R.; Beal, M.F.; Thomas, B. Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications. Trends Neurosci., 2010, 33(12), 541-549.
[http://dx.doi.org/10.1016/j.tins.2010.09.001] [PMID: 20947179]
[14]
Klionsky, D.J. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Biol., 2007, 8(11), 931-937.
[http://dx.doi.org/10.1038/nrm2245] [PMID: 17712358]
[15]
He, P.; Peng, Z.; Luo, Y.; Wang, L.; Yu, P.; Deng, W.; An, Y.; Shi, T.; Ma, D. High-throughput functional screening for autophagy-related genes and identification of TM9SF1 as an autophagosome-inducing gene. Autophagy, 2009, 5(1), 52-60.
[http://dx.doi.org/10.4161/auto.5.1.7247] [PMID: 19029833]
[16]
Fan, X.J.; Wang, Y.; Wang, L.; Zhu, M. Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of PI3K/Akt/mTOR pathway. Oncol. Rep., 2016, 36(6), 3559-3567.
[http://dx.doi.org/10.3892/or.2016.5138] [PMID: 27748934]
[17]
Hatok, J.; Racay, P. Bcl-2 family proteins: master regulators of cell survival. Biomol. Concepts, 2016, 7(4), 259-270.
[http://dx.doi.org/10.1515/bmc-2016-0015] [PMID: 27505095]
[18]
Chen, L.; Meng, Y.; Sun, Q.; Zhang, Z.; Guo, X.; Sheng, X.; Tai, G.; Cheng, H.; Zhou, Y. Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and -independent DR5 upregulation. Cell Death Dis., 2016, 7(8), e2334.
[http://dx.doi.org/10.1038/cddis.2016.234] [PMID: 27512955]
[19]
Zhang, F.; Wang, B.; Long, H.; Yu, J.; Li, F.; Hou, H.; Yang, Q. Decreased miR-124-3p expression prompted breast cancer cell progression mainly by targeting Beclin-1. Clin. Lab., 2016, 62(6), 1139-1145.
[http://dx.doi.org/10.7754/Clin.Lab.2015.151111] [PMID: 27468577]
[20]
Kang, R.; Zeh, H.J.; Lotze, M.T.; Tang, D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ., 2011, 18(4), 571-580.
[http://dx.doi.org/10.1038/cdd.2010.191] [PMID: 21311563]
[21]
Singh, P.; Ravanan, P.; Talwar, P. Death associated protein kinase 1 (DAPK1): A regulator of apoptosis and autophagy. Front. Mol. Neurosci., 2016, 9, 46.
[http://dx.doi.org/10.3389/fnmol.2016.00046] [PMID: 27445685]
[22]
Pimkina, IuS.; Dorosevich, A.E. Role of the tumor suppressor ARF in oncogenesis. Arkh. Patol., 2009, 71(1), 60-63.
[PMID: 19514363]
[23]
Wang, K. Autophagy and apoptosis in liver injury. Cell Cycle, 2015, 14(11), 1631-1642.
[http://dx.doi.org/10.1080/15384101.2015.1038685] [PMID: 25927598]
[24]
Liang, C.; Lee, J.S.; Inn, K.S.; Gack, M.U.; Li, Q.; Roberts, E.A.; Vergne, I.; Deretic, V.; Feng, P.; Akazawa, C.; Jung, J.U. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat. Cell Biol., 2008, 10(7), 776-787.
[http://dx.doi.org/10.1038/ncb1740] [PMID: 18552835]
[25]
He, C.; Klionsky, D.J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet., 2009, 43, 67-93.
[http://dx.doi.org/10.1146/annurev-genet-102808-114910] [PMID: 19653858]
[26]
Liao, Y.J.; Lee, Y.H.; Chang, F.L.; Ho, H.; Huang, C.H.; Twu, Y.C. The SHP2-ERK2 signaling pathway regulates branched I antigen formation by controlling the binding of CCAAT/enhancer binding protein α to the IGnTC promoter region during erythroid differentiation. Transfusion, 2016, 56(11), 2691-2702.
[http://dx.doi.org/10.1111/trf.13796] [PMID: 27600951]
[27]
Lu, G.D.; Ang, Y.H.; Zhou, J.; Tamilarasi, J.; Yan, B.; Lim, Y.C.; Srivastava, S.; Salto-Tellez, M.; Hui, K.M.; Shen, H.M.; Nguyen, L.N.; Tan, B.C.; Silver, D.L.; Hooi, S.C. CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation-induced cell death in hepatocellular carcinoma. Hepatology, 2015, 61(3), 965-978.
[http://dx.doi.org/10.1002/hep.27593] [PMID: 25363290]
[28]
Tao, M.; Shi, X.Y.; Yuan, C.H.; Hu, J.; Ma, Z.L.; Jiang, B.; Xiu, D.R.; Chen, Y.Y. Expression profile and potential roles of EVA1A in normal and neoplastic pancreatic tissues. Asian Pac. J. Cancer Prev., 2015, 16(1), 373-376.
[http://dx.doi.org/10.7314/APJCP.2015.16.1.373] [PMID: 25640383]
[29]
Rashmi, R.; Pillai, S.G.; Vijayalingam, S.; Ryerse, J.; Chinnadurai, G. BH3-only protein BIK induces caspase-independent cell death with autophagic features in Bcl-2 null cells. Oncogene, 2008, 27(10), 1366-1375.
[http://dx.doi.org/10.1038/sj.onc.1210783] [PMID: 17873911]
[30]
Lee, E.; Wei, Y.; Zou, Z.; Tucker, K.; Rakheja, D.; Levine, B.; Amatruda, J. F. Genetic inhibition of autophagy promotes p53 loss-of-heterozygosity and tumorigenesis. Oncotarget, 2016, 7(42), 67919-67933.
[http://dx.doi.org/10.18632/oncotarget.12084]
[31]
Zhang, Q.Y.; Jin, R.; Zhang, X.; Sheng, J.P.; Yu, F.; Tan, R.X.; Pan, Y.; Huang, J.J.; Kong, L.D. The putative oncotarget CSN5 controls a transcription-uncorrelated p53-mediated autophagy implicated in cancer cell survival under curcumin treatment. Oncotarget, 2016, 7(43), 69688-69702.
[http://dx.doi.org/10.18632/oncotarget.11940] [PMID: 27626169]
[32]
Ciavarra, G.; Zacksenhaus, E. Direct and indirect effects of the pRb tumor suppressor on autophagy. Autophagy, 2011, 7(5), 544-546.
[http://dx.doi.org/10.4161/auto.7.5.15056] [PMID: 21325879]
[33]
Jia, W.; Yu, T.; Cao, X.; An, Q.; Yang, H. Clinical effect of DAPK promoter methylation in gastric cancer: A systematic meta-analysis. Medicine (Baltimore), 2016, 95(43), e5040.
[http://dx.doi.org/10.1097/MD.0000000000005040] [PMID: 27787359]
[34]
Qu, X.; Yu, J.; Bhagat, G.; Furuya, N.; Hibshoosh, H.; Troxel, A.; Rosen, J.; Eskelinen, E.L.; Mizushima, N.; Ohsumi, Y.; Cattoretti, G.; Levine, B. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest., 2003, 112(12), 1809-1820.
[http://dx.doi.org/10.1172/JCI20039] [PMID: 14638851]
[35]
Coppola, D.; Khalil, F.; Eschrich, S.A.; Boulware, D.; Yeatman, T.; Wang, H.G. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer, 2008, 113(10), 2665-2670.
[http://dx.doi.org/10.1002/cncr.23892] [PMID: 18833585]
[36]
Li, L.; Khatibi, N.H.; Hu, Q.; Yan, J.; Chen, C.; Han, J.; Ma, D.; Chen, Y.; Zhou, C. Transmembrane protein 166 regulates autophagic and apoptotic activities following focal cerebral ischemic injury in rats. Exp. Neurol., 2012, 234(1), 181-190.
[http://dx.doi.org/10.1016/j.expneurol.2011.12.038] [PMID: 22227058]
[37]
Shu, S.; Li, C.M.; You, Y.L.; Qian, X.L.; Zhou, S.; Ling, C.Q. Electroacupuncture Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulation of Autophagy and Apoptosis. Evid. Based Complement. Alternat. Med., 2016, 2016, 7297425.
[http://dx.doi.org/10.1155/2016/7297425] [PMID: 27800003]
[38]
Deng, Y.H.; He, H.Y.; Yang, L.Q.; Zhang, P.Y. Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke. Neural Regen. Res., 2016, 11(7), 1108-1114.
[http://dx.doi.org/10.4103/1673-5374.187045] [PMID: 27630694]
[39]
Yuan, Y.; Fang, M.; Wu, C.Y.; Ling, E.A. Scutellarin as a Potential Therapeutic Agent for Microglia-Mediated Neuroinflammation in Cerebral Ischemia. Neuromolecular Med., 2016, 18(3), 264-273.
[http://dx.doi.org/10.1007/s12017-016-8394-x] [PMID: 27103430]
[40]
Zhao, Y.; Huang, Q.; Yang, J.; Lou, M.; Wang, A.; Dong, J.; Qin, Z.; Zhang, T. Autophagy impairment inhibits differentiation of glioma stem/progenitor cells. Brain Res., 2010, 1313, 250-258.
[http://dx.doi.org/10.1016/j.brainres.2009.12.004] [PMID: 20004652]
[41]
Nassif, M.; Hetz, C. Targeting autophagy in ALS: a complex mission. Autophagy, 2011, 7(4), 450-453.
[http://dx.doi.org/10.4161/auto.7.4.14700] [PMID: 21252621]
[42]
Li, M.; Lu, G.; Hu, J.; Shen, X.; Ju, J.; Gao, Y.; Qu, L.; Xia, Y.; Chen, Y.; Bai, Y. EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy. Stem Cell Reports, 2016, 6(3), 396-410.
[http://dx.doi.org/10.1016/j.stemcr.2016.01.011] [PMID: 26905199]
[43]
Cavallucci, V.; Fidaleo, M.; Pani, G. Neural Stem Cells and Nutrients: Poised Between Quiescence and Exhaustion. Trends Endocrinol. Metab., 2016, 27(11), 756-769.
[http://dx.doi.org/10.1016/j.tem.2016.06.007] [PMID: 27387597]

Rights & Permissions Print Cite
Article Metrics
20
1
© 2024 Bentham Science Publishers | Privacy Policy