Characterizing the Role of SMYD2 in Mammalian Embryogenesis—Future Directions
Abstract
:1. Introduction
2. SMYD2 in Cancer
3. SMYD2 in Embryogenesis
3.1. SMYD2 in the WNT Pathway and Mesendodermal Differentiation
3.2. SMYD2 in Hematopoiesis and Leukemia
3.3. SMYD2 in the Hypothalamus and Vomeronasal Organ (VNO)
4. Conclusions and Future Directions
Funding
Conflicts of Interest
References
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Target Protein | Protein Function | Associated Cancers | Refs. |
---|---|---|---|
Heat shock protein 90 (HSP90) | Titin stability and sarcomere assembly in muscle tissue, drives handling of several oncoproteins | Lung, breast, urothelial, colorectal, bladder carcinomas | [25,26,27,28] |
Signal transducer and activator of transcription-3 (STAT3) | Becomes activated in complex with SMYD2, p65, and NF-kB, transcription activator, feed-forward SMYD2 expression, increased proliferation, stem cell self-renewal | Breast carcinomas, leukemias | [29] |
Histone 3 (K4) | Interacts with RNA Polymerase II, RNA helicase, drives gene transcription at promotor regions | Lung, breast, glioblastomas | [7,28,30] |
Histone 3 (K36) | Associated with gene bodies, defines exons, recruits HDACs, modulates transcription | Embryonic kidney and fibroblast carcinomas | [5,28,31,32,33] |
p53 (K370) | Cell cycle arrest | p53 dysfunction detected in most cancer types | [7,8,31,33,34] |
β-catenin (K133) | Methylation promotes nuclear translocation and activation of WNT signaling | B-cell precursor acute lymphoblastic leukemia (ALL), colon, breast, and hepatocellular carcinomas | [13,35,36] |
Retinoblastoma tumor suppressor protein (RB1; K810) | Promotes cell cycle progression; G1/S transition | Bladder carcinomas | [10,11] |
Ahnak nucleoprotein 2 | Cell migration and invasion | Chronic myeloid leukemia (CML), Mixed lineage leukemia rearranged adult B-acute lymphoblastic leukemia (MLLr-B-ALL), adult B-acute lymphoblastic leukemia (B-ALL), and T-cell acute lymphoblastic leukemia (T-ALL) | [18,19,37] |
Estrogen receptor-α (ER-α; K266) | Nuclear receptor for sex hormone estrogen, potent upstream activator of gene transcription | Breast | [17] |
Poly-(ADP-ribose) polymerase 1 (PARP1; K528) | Enhances poly (ADP-ribose) activity | Esophageal squamous cell and bladder carcinoma, pediatric acute lymphoblastic leukemia | [16,31,33] |
Phosphatase and tensin homologue (PTEN; K313) | Down-regulates tumor suppressor & activates the phosphatidylinositol 3-kinase-AKT pathway | Prostate, small cell lung cancers | [15] |
Bone Morphogenic Protein Receptor-2 (BMPR2) | Methylation upregulates BMP2 signaling, important for bone development and MSC proliferation | Skin, colorectal, ovarian, breast, embryonic kidney carcinomas | [13] |
Frizzled-2 | STAT3 interaction, epithelial-mesenchymal transition, WNT and Hippo signaling | Hepatocellular | [35,38] |
Erythrocyte membrane protein band 4.1 like (3EBP41L3; K1610) | Tumor suppressor | Breast, non-small-cell lung, brain, ovarian cancers | [39] |
Model | Phenotype | Refs. |
---|---|---|
Nkx2.5 Cre/Smyd2flox/flox (CKO) mice (cardiac-specific) | No phenotype | [7] |
Mx-1Cre/Smyd2flox/flox (CKO) mice (hematopoetic stem cell-specific) | Reduced HSC and downstream progenitor populations via apoptosis and cell cycle blocking | [35] |
Smyd2-/- human embryonic stem cells | Blocked mesendodermal lineage commitment, No affect on self-renewal and neurectoderm | [30] |
morpholino-Smyd2a-/- zebrafish | Developmental delay, tail abnormalities, over-induction of Nodal pathway | [40] |
morpholino-Smyd2a-/- zebrafish | Severe cardiac structural and sarcomeric malformation, tail abnormalities | [25] |
Smyd2-/- (global KO) mice | No developmental phenotype, reduced susceptibility to leukemia | [41] |
CRISPR/Cas9 SMYD2 KO human keratinocytes (in vitro) | Impaired BMP2 morphogen signaling | [14] |
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Jarrell, D.K.; Hassell, K.N.; Crans, D.C.; Lanning, S.; Brown, M.A. Characterizing the Role of SMYD2 in Mammalian Embryogenesis—Future Directions. Vet. Sci. 2020, 7, 63. https://doi.org/10.3390/vetsci7020063
Jarrell DK, Hassell KN, Crans DC, Lanning S, Brown MA. Characterizing the Role of SMYD2 in Mammalian Embryogenesis—Future Directions. Veterinary Sciences. 2020; 7(2):63. https://doi.org/10.3390/vetsci7020063
Chicago/Turabian StyleJarrell, Dillon K., Kelly N. Hassell, Debbie C. Crans, Shari Lanning, and Mark A. Brown. 2020. "Characterizing the Role of SMYD2 in Mammalian Embryogenesis—Future Directions" Veterinary Sciences 7, no. 2: 63. https://doi.org/10.3390/vetsci7020063