Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death

Sun Mi Park; Kwangsoo Kim; Eun Ju Lee; Bo Kyoung Kim; Tae Jin Lee; Taegun Seo; Ik Soon Jang; Sang Hoon Lee; Soohyun Kim; Je Ho Lee; Junsoo Park

doi:10.1016/j.bbrc.2009.10.149

Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death

Sun Mi Park, Kwangsoo Kim, Eun Ju Lee, Bo Kyoung Kim, Tae Jin Lee, Taegun Seo, Ik Soon Jang, Sang Hoon Lee, Soohyun Kim, Je Ho Lee, Junsoo Park

Division of Bioscience and Biotechnology

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

Although the role of autophagy in tumorigenesis remains controversial, recent reports support the notion that inhibition of autophagy promotes tumor formation. Damage-regulated autophagy regulator (DRAM) has been identified as an effector molecule that is critical for p53-mediated apoptosis, and we investigated whether there might be other DRAM-like molecules linking autophagy and apoptosis. In this study, we cloned a novel DRAM-homologous protein, DRAM2, and showed that the expression of DRAM2 is down-regulated in ovarian tumors. DRAM2 is mainly localized in the lysosome, and co-localizes with DRAM. While expression of DRAM or DRAM2 individually did not induce cell death, co-expression of DRAM2 with DRAM significantly induced cell death, while the silencing of endogenous DRAM2 attenuated cell death, suggesting that DRAM2 is involved in cell death. Thus, we propose that reduced expression of DRAM2 may contribute to enhanced cell survival in tumor cells.

Original language	English
Pages (from-to)	1340-1344
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	390
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2009.10.149
Publication status	Published - 2009 Dec 25

Bibliographical note

Funding Information:
We would particularly like to thank Kevin M. Ryan for providing the DRAM expression plasmid. This study was supported by a Science Research Center (Molecular Therapy Research Center) grant from the Korea Science and Engineering Foundation , and by a Korea Basic Science Institute grant (K-MeP). The nucleotide and deduced amino acid sequences of DRAM2 were submitted and registered in GenBank (Accession No. EF710624.1 ).

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death",

abstract = "Although the role of autophagy in tumorigenesis remains controversial, recent reports support the notion that inhibition of autophagy promotes tumor formation. Damage-regulated autophagy regulator (DRAM) has been identified as an effector molecule that is critical for p53-mediated apoptosis, and we investigated whether there might be other DRAM-like molecules linking autophagy and apoptosis. In this study, we cloned a novel DRAM-homologous protein, DRAM2, and showed that the expression of DRAM2 is down-regulated in ovarian tumors. DRAM2 is mainly localized in the lysosome, and co-localizes with DRAM. While expression of DRAM or DRAM2 individually did not induce cell death, co-expression of DRAM2 with DRAM significantly induced cell death, while the silencing of endogenous DRAM2 attenuated cell death, suggesting that DRAM2 is involved in cell death. Thus, we propose that reduced expression of DRAM2 may contribute to enhanced cell survival in tumor cells.",

author = "Park, {Sun Mi} and Kwangsoo Kim and Lee, {Eun Ju} and Kim, {Bo Kyoung} and Lee, {Tae Jin} and Taegun Seo and Jang, {Ik Soon} and Lee, {Sang Hoon} and Soohyun Kim and Lee, {Je Ho} and Junsoo Park",

note = "Funding Information: We would particularly like to thank Kevin M. Ryan for providing the DRAM expression plasmid. This study was supported by a Science Research Center (Molecular Therapy Research Center) grant from the Korea Science and Engineering Foundation , and by a Korea Basic Science Institute grant (K-MeP). The nucleotide and deduced amino acid sequences of DRAM2 were submitted and registered in GenBank (Accession No. EF710624.1 ). ",

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AU - Park, Sun Mi

AU - Kim, Kwangsoo

AU - Lee, Eun Ju

AU - Kim, Bo Kyoung

AU - Lee, Tae Jin

AU - Seo, Taegun

AU - Jang, Ik Soon

AU - Lee, Sang Hoon

AU - Kim, Soohyun

AU - Lee, Je Ho

AU - Park, Junsoo

N1 - Funding Information: We would particularly like to thank Kevin M. Ryan for providing the DRAM expression plasmid. This study was supported by a Science Research Center (Molecular Therapy Research Center) grant from the Korea Science and Engineering Foundation , and by a Korea Basic Science Institute grant (K-MeP). The nucleotide and deduced amino acid sequences of DRAM2 were submitted and registered in GenBank (Accession No. EF710624.1 ).

PY - 2009/12/25

Y1 - 2009/12/25

N2 - Although the role of autophagy in tumorigenesis remains controversial, recent reports support the notion that inhibition of autophagy promotes tumor formation. Damage-regulated autophagy regulator (DRAM) has been identified as an effector molecule that is critical for p53-mediated apoptosis, and we investigated whether there might be other DRAM-like molecules linking autophagy and apoptosis. In this study, we cloned a novel DRAM-homologous protein, DRAM2, and showed that the expression of DRAM2 is down-regulated in ovarian tumors. DRAM2 is mainly localized in the lysosome, and co-localizes with DRAM. While expression of DRAM or DRAM2 individually did not induce cell death, co-expression of DRAM2 with DRAM significantly induced cell death, while the silencing of endogenous DRAM2 attenuated cell death, suggesting that DRAM2 is involved in cell death. Thus, we propose that reduced expression of DRAM2 may contribute to enhanced cell survival in tumor cells.

AB - Although the role of autophagy in tumorigenesis remains controversial, recent reports support the notion that inhibition of autophagy promotes tumor formation. Damage-regulated autophagy regulator (DRAM) has been identified as an effector molecule that is critical for p53-mediated apoptosis, and we investigated whether there might be other DRAM-like molecules linking autophagy and apoptosis. In this study, we cloned a novel DRAM-homologous protein, DRAM2, and showed that the expression of DRAM2 is down-regulated in ovarian tumors. DRAM2 is mainly localized in the lysosome, and co-localizes with DRAM. While expression of DRAM or DRAM2 individually did not induce cell death, co-expression of DRAM2 with DRAM significantly induced cell death, while the silencing of endogenous DRAM2 attenuated cell death, suggesting that DRAM2 is involved in cell death. Thus, we propose that reduced expression of DRAM2 may contribute to enhanced cell survival in tumor cells.

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Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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