| Description | DRAM consists of 238 amino acids. It is predicted to have 6 transmembrane regions. DRAM is a lysosomal protein that is required for induction of autophagy by the p53 pathway. |
| Expression | No expression data for endogenous DRAM is available at the protein level. |
| Localisation | Overexpressed and tagged DRAM appears to localize to the lysosome. Localization of endogenous DRAM has not been reported. |
| Function | The precise function of DRAM is unknown. The first paper reporting a biologic activity for DRAM was in 2006. There is strong evidence from multiple sources that DRAM (FLJ11259) is a direct p53 target gene and is induced in response to DNA damage. This includes global p53-induced gene expression and global p53 ChIP-PET studies. DRAM is a mediator of autophagy and is required for p53-induced apoptosis in response to DNA damage. However, DRAM has minimal effects alone on cell growth or apoptosis. DRAM mRNA is downregulated in some tumors compared to normal. Overall evidence suggests DRAM may be a tumor suppressor downstream of p53. However, whether the role of DRAM in autophagy is positive or negative and whether DRAM mediates cell death or survival in pathologic and physiologic settings may be complex and context dependent. |
| Homology | DRAM is highly conserved in higher metazoans including C. elegans, Drosophila, and Zebrafish. DRAM shares no homology with any proteins of known function. DRAM has no known functional domains. Human DRAM shares significant homology with other 6 transmembrane proteins of unknown function, including TMEM77, TMEM150 (TM6P1), and FLJ12993. TM6P1 was cloned by subtractive hybridization as induced in starved rat liver. Nutrient starvation is a major physiologic inducer of autophagy. |
| Identification of a new gene (rat TM6P1) encoding a fasting-inducible, integral membrane protein with six transmembrane domains. |
| Zhang J, D'Ercole AJ, Underwood LE. |
| Biochim Biophys Acta. 2000 Jun 21;1492(1):280-4. |
| PMID 10858565 |
| |
| A p53-dominant transcriptional response to cisplatin in testicular germ cell tumor-derived human embryonal carcinoma. |
| Kerley-Hamilton JS, Pike AM, Li N, DiRenzo J, Spinella MJ. |
| Oncogene. 2005 Sep 8;24(40):6090-100. |
| PMID 15940259 |
| |
| DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. |
| Crighton D, Wilkinson S, O'Prey J, Syed N, Smith P, Harrison PR, Gasco M, Garrone O, Crook T, Ryan KM. |
| Cell. 2006 Jul 14;126(1):121-34. |
| PMID 16839881 |
| |
| p53 and metabolism: Inside the TIGAR. |
| Green DR, Chipuk JE. |
| Cell. 2006 Jul 14;126(1):30-2. |
| PMID 16839873 |
| |
| A global map of p53 transcription-factor binding sites in the human genome. |
| Wei CL, Wu Q, Vega VB, Chiu KP, Ng P, Zhang T, Shahab A, Yong HC, Fu Y, Weng Z, Liu J, Zhao XD, Chew JL, Lee YL, Kuznetsov VA, Sung WK, Miller LD, Lim B, Liu ET, Yu Q, Ng HH, Ruan Y. |
| Cell. 2006 Jan 13;124(1):207-19. |
| PMID 16413492 |
| |
| p73 regulates DRAM-independent autophagy that does not contribute to programmed cell death. |
| Crighton D, O'Prey J, Bell HS, Ryan KM. |
| Cell Death Differ. 2007 Jun;14(6):1071-9. Epub 2007 Feb 16. |
| PMID 17304243 |
| |
| DRAM links autophagy to p53 and programmed cell death. |
| Crighton D, Wilkinson S, Ryan KM. |
| Autophagy. 2007 Jan-Feb;3(1):72-4. Epub 2007 Jan 28. |
| PMID 17102582 |
| |
| The direct p53 target gene, FLJ11259/DRAM, is a member of a novel family of transmembrane proteins. |
| Kerley-Hamilton JS, Pike AM, Hutchinson JA, Freemantle SJ, Spinella MJ. |
| Biochim Biophys Acta. 2007 Apr;1769(4):209-19. Epub 2007 Feb 22. |
| PMID 17397945 |
| |