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Literature summary for 3.6.4.13 extracted from

  • Hashemi, V.; Masjedi, A.; Hazhir-Karzar, B.; Tanomand, A.; Shotorbani, S.S.; Hojjat-Farsangi, M.; Ghalamfarsa, G.; Azizi, G.; Anvari, E.; Baradaran, B.; Jadidi-Niaragh, F.
    The role of DEAD-box RNA helicase p68 (DDX5) in the development and treatment of breast cancer (2019), J. Cell. Physiol., 234, 5478-5487 .
    View publication on PubMed

Application

Application Comment Organism
drug development enzyme p68 is a drug target in the treatment of cancer, e.g. breast cancer Homo sapiens
medicine analysis of tumorigenic function of p68 in association with its targeting potential for the treatment of breast cancer Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene DDX5, is located in the region 17q23-q25 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
4-(3,5-dimethoxyphenyl)-N-(7-fluoro-3-methoxyquinoxalin-2-yl)piperazine-1-carboxamide i.e. supinoxin or RX-5902, intervenes in the phosphorylated p68-beta-catenin signaling pathway by interacting with Tyr593 in SK-MEL-28 (human melanoma), MDA-MB-231 (human metastatic breast cancer), and WI-38 (human normal fetal lung fibroblasts) cell lines Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O Homo sapiens
-
ADP + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P17844
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
acetylation P68 may undergo various modifications such as ubiquitylation, sumoylation, and acetylation Homo sapiens
phosphoprotein phosphorylation of tyrosine in p68 enhances cell transformation and cancer cell migration. The Y593 phosphorylation of p68 promotes the detachment of histone deacetylase (HDAC) 1 from the Snail1 promoter, which leads to the expression of Snail1. The phosphorylation of particular sites (such as Y593 and Y595 induced by PDGF) in p68 can attenuate resistance to TRAIL-induced apoptosis. The phosphorylated p68 exerts a definite protective effect on the activities of cancer cells. Phosphorylated p68 can enter the cytoplasm, which leads to its interaction with beta-catenin and displacment of axin Homo sapiens
sumoylation P68 may undergo various modifications such as ubiquitylation, sumoylation, and acetylation. P68 may be sumoylated on site K53 residue, which may be associated with transcriptional coactivation Homo sapiens
ubiquitination P68 may undergo various modifications such as ubiquitylation, sumoylation, and acetylation Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell deregulated expression of p68 in breast cancer. The DDX5 locus is consistently strengthened in breast cancer and is usually overexpressed in association with ERBB2. Various breast cancer cell lines exhibit different dependence on DDX5 expression Homo sapiens
-
carcinoma cell p68 is highly expressed in several carcinomas, such as breast, prostate, and colon Homo sapiens
-
EFM-19 cell
-
Homo sapiens
-
fibroblast fetal lung fibroblasts Homo sapiens
-
MDA-MB-231 cell
-
Homo sapiens
-
MDA-MB-453 cell
-
Homo sapiens
-
melanoma cell
-
Homo sapiens
-
SK-BR-3 cell
-
Homo sapiens
-
SK-MEL-28 cell
-
Homo sapiens
-
WI-38 cell
-
Homo sapiens
-
ZR-75-1 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O
-
Homo sapiens ADP + phosphate
-
?

Synonyms

Synonyms Comment Organism
ATP-dependent RNA helicase DDX5
-
Homo sapiens
DDX5
-
Homo sapiens
DEAD-box RNA helicase
-
Homo sapiens
p68
-
Homo sapiens
RNA Helicase p68
-
Homo sapiens

General Information

General Information Comment Organism
evolution RNA helicase p68 or DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5) is a unique member of the highly conserved protein family, which is involved in a broad spectrum of biological processes, including transcription, translation, precursor messenger RNA processing or alternative splicing, and microRNA (miRNA) processing Homo sapiens
malfunction p68 can bind to the acetyl transferase p300 and facilitate the p300-mediated acetylation, irregular activation of p68 disrupts the binding, which leads to the interaction with HDACs. Silencing p68 by shRNAs inhibits the proliferation of four distinct breast cancer cell lines (MDA-MB-453, SK-BR-3, EFM19, and ZR-75-1). Knockdown of the DDX5 in the breast cancer cell lines whose expansion is required for its upregulation exerts more inhibitory effects compared with those cell lines whose expansion does not require DDX5. Abnormal expression of p68 in tumor may be in part due to c-Myc-dependent Wnt signaling, overview. Silencing of either beta-catenin or c-Myc leads to downregulation of the Wnt3a-dependent p68 overexpression Homo sapiens
physiological function p68 is necessary for cell growth and participates in the early development and maturation of some organs. Interestingly, p68 is a transcriptional coactivator of numerous oncogenic transcription factors, including nuclear factor-kappabeta (NF-kappabeta), estrogen receptor alpha (ERalpha), beta-catenin, androgen receptor, Notch transcriptional activation complex, p53 and signal transducer, and activator of transcription 3 (STAT3). Role of p68 (DDX5) in multiple dysregulated cellular processes in various cancers and its abnormal expression indicate the importance of this factor in tumor development, overview. The role of p68 in cancer is complex and depends on the cellular microenvironment and interacting factors. Translocation of p68 to the promoters of tumor-promoting factors, such as cyclin D1 and c-Myc, and their activation converts them to transcription initiator. P68 as a coactivator of AF1 induces the proliferation of breast cancer cells. p68 modulates the expression of target genes in part through interaction with long noncoding RNAs. P68 exhibits a close relation with TCF4-beta-catenin in the MCF7, MDA-MB 231, and 4T1 breast cancer cell lines. P68 is a coactivator of p53 and modulates the p53 DNA damage response in breast cancer cell line MCF-7. Various breast cancer cell lines exhibit different dependence on DDX5 expression. P68 can manage cell cycle progression in cancer cell. P68 is also involved in the development of neural or mesodermal tissues, and needed for growth regulation Homo sapiens