Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death.
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.
Park
Sun-Mi
SM
Yonsei University, Division of Biological Science and Technology, Wonju 220-100, Republic of Korea.
Kim
Kwangsoo
K
Lee
Eun-Ju
EJ
Kim
Bo-Kyoung
BK
Lee
Tae Jin
TJ
Seo
Taegun
T
Jang
Ik-Soon
IS
Lee
Sang-Hoon
SH
Kim
Soohyun
S
Lee
Je-Ho
JH
Park
Junsoo
J
D000595:Amino Acid Sequence; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D020868:Gene Silencing; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
C544299:DRAM2 protein, human; D008565:Membrane Proteins