Abstract
The lysine-specific demethylase 1 (LSD1), a component of several histone deacetylase complexes, plays an important role in chromatin remodeling and transcriptional regulation. Here, we generated multiple cell lines in which LSD1 is inducibly expressed or knocked down and found that LSD1 is required for cell proliferation. In addition, we found that deficiency in LSD1 leads to a partial cell cycle arrest in G2/M and sensitizes cells to growth suppression induced by DNA damage or MDM2 inhibition in a p53-dependent manner. We also showed that LSD1 deficiency delays p53 stabilization induced by DNA damage, leading to a delayed induction of p21 and MDM2. Finally, we performed a microarray study and identified several novel LSD1 target genes, including S100A8, which encodes a calcium-binding protein, and DEK, a proto-oncogene. Taken together, we uncovered that LSD1 has a pro-oncogenic function by modulating pro-survival gene expression and p53 transcriptional activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 15471-15475 |
| Number of pages | 5 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 21 |
| DOIs | |
| State | Published - May 25 2007 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners. / Scoumanne, Ariane; Chen, Xinbin.
In: Journal of Biological Chemistry, Vol. 282, No. 21, 25.05.2007, p. 15471-15475.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners
AU - Scoumanne, Ariane
AU - Chen, Xinbin
PY - 2007/5/25
Y1 - 2007/5/25
N2 - The lysine-specific demethylase 1 (LSD1), a component of several histone deacetylase complexes, plays an important role in chromatin remodeling and transcriptional regulation. Here, we generated multiple cell lines in which LSD1 is inducibly expressed or knocked down and found that LSD1 is required for cell proliferation. In addition, we found that deficiency in LSD1 leads to a partial cell cycle arrest in G2/M and sensitizes cells to growth suppression induced by DNA damage or MDM2 inhibition in a p53-dependent manner. We also showed that LSD1 deficiency delays p53 stabilization induced by DNA damage, leading to a delayed induction of p21 and MDM2. Finally, we performed a microarray study and identified several novel LSD1 target genes, including S100A8, which encodes a calcium-binding protein, and DEK, a proto-oncogene. Taken together, we uncovered that LSD1 has a pro-oncogenic function by modulating pro-survival gene expression and p53 transcriptional activity.
AB - The lysine-specific demethylase 1 (LSD1), a component of several histone deacetylase complexes, plays an important role in chromatin remodeling and transcriptional regulation. Here, we generated multiple cell lines in which LSD1 is inducibly expressed or knocked down and found that LSD1 is required for cell proliferation. In addition, we found that deficiency in LSD1 leads to a partial cell cycle arrest in G2/M and sensitizes cells to growth suppression induced by DNA damage or MDM2 inhibition in a p53-dependent manner. We also showed that LSD1 deficiency delays p53 stabilization induced by DNA damage, leading to a delayed induction of p21 and MDM2. Finally, we performed a microarray study and identified several novel LSD1 target genes, including S100A8, which encodes a calcium-binding protein, and DEK, a proto-oncogene. Taken together, we uncovered that LSD1 has a pro-oncogenic function by modulating pro-survival gene expression and p53 transcriptional activity.
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UR - http://www.scopus.com/inward/citedby.url?scp=34447519212&partnerID=8YFLogxK
U2 - 10.1074/jbc.M701023200
DO - 10.1074/jbc.M701023200
M3 - Article
C2 - 17409384
AN - SCOPUS:34447519212
VL - 282
SP - 15471
EP - 15475
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 21
ER -