ASXL1 represses retinoic acid receptor-mediated transcription through associating with HP1 and LSD1.

Lee, Sang-Wang; Cho, Yang-Sook; Na, Jung-Min; Park, Ui-Hyun; Kang, Myengmo; Kim, Eun-Joo; Um, Soo‐Jong

doi:10.1074/jbc.a109.065862

Cited by 15 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combined loss of ASXL1 and TET2 increases myeloid disease severity [83,91]. In addition, it has been demonstrated that the histone demethylase LSD1 cooperates with ASXL1 in its transcriptional repression activity by removing histone H3 Lys4 methylation (an active histone mark) through interacting with the N-terminal region of ASXL1 [92].…”

Section: Additional Sex Combs-like 1 (Asxl1) Mutationsmentioning

confidence: 99%

Epigenetic alterations in acute myeloid leukemias

2014

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a heterogeneous disease for which the standard treatment with cytotoxic chemotherapy has remained largely unchanged for over four decades, with unfavorable clinical results. Epigenetic alterations have been described in several AMLs, and in some cases their origin has been studied in detail mechanistically (such as in acute promyelocytic leukemia, caused by the promyelocytic leukemia-retinoic acid receptor-a fusion protein). Recently, the advent of massive parallel sequencing has revealed that > 70% of AML cases have mutations in DNA methylation-related genes or mutations in histone modifiers, showing that epigenetic alterations are key players in the development of most, if not all, AMLs, and pointing to the exploitation of new molecular targets for more efficacious therapies. This review provides a brief overview of the latest findings on the characterization of the epigenetic landscape of AML and discusses the rationale for the optimization of epigenetic therapy of AML.

show abstract

Section: Additional Sex Combs-like 1 (Asxl1) Mutationsmentioning

confidence: 99%

Epigenetic alterations in acute myeloid leukemias

2014

View full text Add to dashboard Cite

show abstract

“…In the absence of an agonist such as ATRA, RA receptors bind to RXR and recruit the nuclear receptor corepressor or silencing mediator for retinoid and thyroid hormone receptors along with epifactors such as histone deacetylases or DNA methyltransferases to repress gene expression (29,30). A recent study suggests that LSD1 also contributes to RAR␣-mediated transcription via repressive histone H3 methylation (31). Because SALL4 directly interacts with RAR␣ and also dynamically recruits these epifactors, it would inhibit AML differentiation via suppressing the RAR␣ pathway.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of SALL4 Protein Enhances All-trans Retinoic Acid-induced Cellular Differentiation in Acute Myeloid Leukemia Cells

Liu

Leung

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: SALL4 plays important roles in hematopoiesis and leukemogenesis, including at the stem cell level. Results: SALL4 blocks ATRA-mediated differentiation through directly suppressing RA receptor ␣ signaling. Conclusion: SALL4 plays an unfavorable role in ATRA-based regimes. Significance: SALL4 contributes to AML pathogenesis by inhibiting differentiation stimuli, reinforcing its role as a therapeutic target in leukemia.

show abstract

“…The resulting ternary complex of HP1, ASXL1, and LSD1 works together in transcriptional suppression. In the ternary complex on chromatin, HP1 may be related to methylated H3K9 and protect the methyl group from LSD1 attack without affecting LSD1‐catalyzed demethylation of H3K4, leaving net methylated H3K9 for transcriptional repression . Mulligan et al.…”

Section: Biochemistry Of Lsd1mentioning

confidence: 99%

“…In the ternary complex on chromatin, HP1 may be related to methylated H3K9 and protect the methyl group from LSD1 attack without affecting LSD1-catalyzed demethylation of H3K4, leaving net methylated H3K9 for transcriptional repression. 70 Mulligan et al reported that the amino acid residues 165-276 of LSD1, the SWIRM binding domain, seem to symbolize a least SIRT1 (NAD-dependent deacetylase sirtuin-1) binding field (amino acid residues 231-510). When there is no Notch signaling, the SIRT1-LSD1 core complex constituents are engaged in a CtBP1-dependent way to the genes controlled by the Notch signaling pathway promoter to coordinately support the establishment of a repressive pattern of histone marks and to repress their expression.…”

Section: Nonhistone Substrates Of Lsd1 and Protein-protein Interacmentioning

confidence: 99%

A Systematic Review of Histone Lysine‐Specific Demethylase 1 and Its Inhibitors

Zheng¹,

Wang²,

Li³

et al. 2015

Medicinal Research Reviews

163

130

View full text Add to dashboard Cite

Histone lysine-specific demethylase 1 (LSD1) is the first discovered and reported histone demethylase by Dr. Shi Yang's group in 2004. It is classified as a member of amine oxidase superfamily, the common feature of which is using the flavin adenine dinucleotide (FAD) as its cofactor. Since it is located in cell nucleus and acts as a histone methylation eraser, LSD1 specifically removes mono- or dimethylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been indicated that LSD1 and its downstream targets are involved in a wide range of biological courses, including embryonic development and tumor-cell growth and metastasis. LSD1 has been reported to be overexpressed in variety of tumors. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development. LSD1 targeting inhibitors may represent a new insight in anticancer drug discovery. This review summarizes recent studies about LSD1 and mainly focuses on the basic physiological function of LSD1 and its involved mechanisms in pathophysiologic conditions, as well as the development of LSD1 inhibitors as potential anticancer therapeutic agents.

show abstract

ASXL1 represses retinoic acid receptor-mediated transcription through associating with HP1 and LSD1.

Cited by 15 publications

References 0 publications

Epigenetic alterations in acute myeloid leukemias

Epigenetic alterations in acute myeloid leukemias

Knockdown of SALL4 Protein Enhances All-trans Retinoic Acid-induced Cellular Differentiation in Acute Myeloid Leukemia Cells

A Systematic Review of Histone Lysine‐Specific Demethylase 1 and Its Inhibitors

Contact Info

Product

Resources

About