Article Evaluation The Wikipedia article that I am doing an evaluation on is methylation. Majority of the article is concise and to the point, little space for distraction. What I did find was there is information missing that should be added, for instance, that DNA methylation is usually associated with gene silencing. Another notable issue is the lack of a section on Histone methylation and the background behind the process. The claim is neutral and there is no bias in the paragraphs and sections. The article is rated at a C and is part of the wikiproject genetics. Methylation is an area of study that still has a lot to learn about but I feel the page is missing information that could be presented and shared with the public and is found in scientific literature. Citations are still needed in the wiki page as there are paragraph sections without citations. After clicking on a few references the links send me to the paper the information came from and there is relevance in the paper, but some more references and scientific documents are needed. The page discusses the process of methylation as discussed in class, but is missing some information discussed in lecture such as histone methylation and a deeper look at DNA methylation.
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Good job. Keep it up! AdamCF87 (talk) 17:36, 5 October 2017 (UTC)
My topic for my Wiki project is possibly, A-DNA. One source I will use is the Biochemistry 3381, 3382 textbook that I will cite in Sandbox. I plan on adding more information about A-DNA and finding scholarly articles that relate to research involved with A-DNA as well as structural information and biological basis of A-DNA.
A-DNA is generally shorter and wider than B-DNA, Pitch length is 2.46nm for A-DNA and 3.4nm for B-DNA
Bases are not perpendicular to the helical axis in A-DNA but are tilted 19° to the helical axis
Successive base pairs are ever 0.23nm along the axis, whereas they are 0.332nm in B-DNA.
Regular B-DNA can adopt the A-DNA conformation when dehydrated.
Topic has potential. However, while the textbook is an acceptable source, try and use primary sources (eg journal articles). The textbook likely has provided primary references for A-base. It's better to use those. Also, come up with 2 or 3 alternative topics as backups. Otherwise, keep it up. AdamCF87 (talk) 14:43, 17 October 2017 (UTC)
Change of topic, now working on BAALC. This is a human gene which is associated with AML and ALL
BAALC
editBAALC is a gene that codes for the: brain and acute leukemia cytoplasmic protein.[1] The official symbol (BAALC) and official name (brain and acute leukemia cytoplasmic) are maintained by the HGNC.[2] The function of BAALC is not fully understood yet but has been suggested to have synaptic roles involving the post synaptic lipid raft.[3] Lipid rafts are microdomains that are enriched with cholesterol and sphingolipids, lipid raft functions include membrane trafficking, signal processing, and regulation of the actin cytoskeleton.[3] The postsynpatic lipid raft possesses many proteins and is one of the major sites for signal processing and postsynaptic density (PSD).[3] Along with its involvement in the post synaptic lipid rafts, BAALC expression has been associated with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia.[1]
Genetics
edit
BAALC gene is located on the long arm (q) of chromosome 8 at position 22.3 (8q22.3). The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids. [4][5]
The BAALC gene is highly conserved in mammals, domestic pigs, mice and rats.[1] But BAALC is not seen in lower organisms such as: Drosophila. melanogaster, Saccharomyces. cerevisiae, and Caenorhabditis. elegans.[1]
BAALC and its protein are expressed highly in neural tissues such as the Central Nervous System (CNS) and the Spinal Cord, and less expressed in neuroectodermal-derived tissues like the adrenal glands.[6] [1] The BAALC protein is not expressed in peripheral blood leukocytes (PBL), lymph nodes, or nonneural tissues.[1][6][4] BAALC expression was only found in Bone Marrow (BM) when expressed from CD34+ progenitor cells, besides this BAALC expression was not seen.[1] The expression of BAALC from the CD34+ progenitor cells suggest the gene has neuroectodermal and hematopoietic cell functions.[7][1][8] BAALC expression is higher in neuroectodermal-derived tissues such as the frontal part of the brain, more specifically in the hippocampus, and neocortex.[3]
The BAALC gene has eight different transcripts that result into five different protein isoforms.[6] Isoforms that carry the exon number two do not express protein and it is believed that the termination in exon two results in an unstable protein after translation.[1] The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in the above-mentioned mammals.[1]
Function
editThe BAALC gene initially was discovered in the neuroderm derived tissues of both the human and the mouse.[1] The function of BAALC protein is not understood very well, but it is predicted to be associated with the cytoskeleton network.[1] When expressed in Bone Marrow CD34+ progenitor cells BAALC has neuroectodermal and hematopoietic cell functions.[1] Differentiation failure caused by cell shape, motility and adhesion in association between cells are all possible outcomes due to the little known effects and unlear mechanism sites of the BAALC genes.[9] The role of the BAALC gene causing leukemia in immature acute leukemic cells was found by knocking out the function of BAALC gene using hairpin (stem loop) RNA in a human leukemia cell line KG1a.[10] The result of knocking out BAALC expression was a decrease in uncontrolled cell growth and an increase in programmed cell death.[10][9] The BAALC protein isoform 1-6-8, has been found to interact and associate with the CAMK2 alpha subunit and not with the beta subunit.[3] The interaction with the CAMK2 alpha subunit is in the CAMK2 protein's regulatory region and near the autophosphorylation site, this suggested a regulatory function of the 1-6-8 isoform on the alpha subunit.[3] BAALC 1-6-8 isoform also gets targeted to post synaptic lipid rafts which are thought to have functions involved in: signal processing, membrane trafficking, and regulation of the actin cytoskeleton.[3] BAALC may play a role in the regulation of the CAMKII protein through interactions with the alpha subunit, no interactions have been found with the beta subunit of this protein.[3] Evidence has shown the BAALC protein to be an intracellular protein with cytoskeleton network roles, these roles include regulation of the actin cytoskeleton which is an associated role of postsynaptic lipid rafts.[1][3]
Clinical Significance
editIn studies it has been found that overexpression of BAALC is seen in 28% of people with AML and 65% of people with ALL.[1] BAALC is ruled out as a marker for neoplasia because it is not expressed in other cancer cells.[1] BAALC is seen in acute leukemia in immature myoblasts and early progenitor cells, but is excluded from mature hematopoietic cells.[11][1] It has been found in studies that acute myeloid leukemia patients who over expressed BAALC (BAALC Positive) had a median of approximately 5 months of event free survival but those who were BAALC negative had a median of around 15 months, these results were statistically significant.[1] Research has when BAALC was combined with the oncogene Hoxa9, BAALC blocked myeloid differentiation.[11] This blocking caused leukemogenesis. BAALC over-expression has been associated with IDH1 and IDH2 wild type in Chinese cytogenetically normal acute myeloid leukemia patients.[12] The results found by Zhou et al. are different than that found by Weber et al. where no difference in mutations in IDH1 and IDH2 where seen depending on expression of BAALC.[13] Researcher conducted gene expression profiles (GEP) with BAALC and found another gene involved in leukemia, IGFBP7.[14] This gene has BAALC characteristics and, unlike BAALC, may have a role in drug resistance and the mechanism of leukemogenesis.[14] It has been found that treatment for some acute leukemias has failed due to BAALC and this suggests BAALC to be a potential surrogate marker.[14] The use of BAALC expression in acute leukemia prognosis is unclear and being studied.[8][7] Prognosis of patients with AML and BAALC over-expression has been found to be poor or worse than poor.[8] Over-expression of the BAALC gene and considerable accumulation of the gene production has been found to have caused drug resistance in patients.[8]
Expression in Cancers
edit| Cancer | Under or Over expression | Evaluation Method | Reference |
|---|---|---|---|
| Acute Myeloid Leukemia (AML) | Over Expression | RT-PCR | [1] |
| Acute Lymphoblastic Leukemia (ALL) | Over Expression | RT-PCR | [1] |
Overexpression of the BAALC gene is seen in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL).[14][13] It has been found that BAALC can cause the start of Leukemia (leukemogenesis) by stopping the differentiation of myeloid.[11] Silencing BAALC lowers the amount of proliferation and increased cell death (apoptosis) in leukemic cell lines.[10] It has also been found with over-expression of the BAALC genes to cause low levels of complete remission in cancer patients, and low amount of of overall survival.[9]
Structure
editThe human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids. [4][5] This gene codes for eight different transcripts that are translated into six different protein isoforms.[1][15] Isoforms containing exon number two (1-2-6-8 and 1-2-5-6-8) do not code protein and so exon two contains a termination codon.[1]
BAALC protein isoform 1-6-8 is modified by myristoylation an palmitoylation at the N-terminal.[3] These modifications occur on the Glycine 2 and Cysteine 3 amino acids of the protein.[3] These modifications are used for targeting the protein to the lipid rafts.[3] Little phosphorylation of the BAALC isoform 1-6-8 by the CAMK2 protein has been found as well.[3]
Interactions
editSee Also
editCAMK2A[3]
Acute Myeloid Leukemia[1]
Acute lymphoblastic Leukemia[1]
CD34[1]
IGFBP7[14]
References
edit- ^ a b c d e f g h i j k l m n o p q r s t u v w x y Tanner, Stephan M.; Austin, Jamie L.; Leone, Gustavo; Rush, Laura J.; Plass, Christoph; Heinonen, Kristiina; Mrózek, Krzysztof; Sill, Heinz; Knuutila, Sakari (2001-11-20). "BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia". Proceedings of the National Academy of Sciences. 98 (24): 13901–13906. doi:10.1073/pnas.241525498. ISSN 0027-8424. PMC 61139. PMID 11707601.
- ^ "Tissue expression of BAALC - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-11-15.
- ^ a b c d e f g h i j k l m n Wang, Xin; Tian, Qing-Bao; Okano, Akira; Sakagami, Hiroyuki; Moon, Il Soo; Kondo, Hisatake; Endo, Shogo; Suzuki, Tatsuo (2005-02-01). "BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with α, but not β, subunit of Ca2+/calmodulin-dependent protein kinase II". Journal of Neurochemistry. 92 (3): 647–659. doi:10.1111/j.1471-4159.2004.02902.x. ISSN 1471-4159. PMID 15659234. S2CID 23562935.
- ^ a b c d Database, GeneCards Human Gene. "BAALC Gene - GeneCards | BAALC Protein | BAALC Antibody". www.genecards.org. Retrieved 2017-11-15.
- ^ a b c "24997-1-AP". www.ptglab.com. Retrieved 2017-11-15.
- ^ a b c "OMIM Entry - * 606602 - BRAIN AND ACUTE LEUKEMIA GENE, CYTOPLASMIC; BAALC". omim.org. Retrieved 2017-11-15.
- ^ a b Damm, Frederik (April 28, 2011). "Integrative prognostic risk score in acute myeloid leukemia with normal karyotype" (PDF). Blood. 117 (17): 4561–4568. doi:10.1182/blood-2010-08-303479. PMID 21372155. Retrieved November 15, 2017.
- ^ a b c d XIAO, SHI-JI; SHEN, JIAN-ZHEN; HUANG, JIN-LONG; FU, HAI-YING (2015-7). "Prognostic significance of the BAALC gene expression in adult patients with acute myeloid leukemia: A meta-analysis". Molecular and Clinical Oncology. 3 (4): 880–888. doi:10.3892/mco.2015.562. ISSN 2049-9450. PMC 4486884. PMID 26171200.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c XIAO, SHI-JI; SHEN, JIAN-ZHEN; HUANG, JIN-LONG; FU, HAI-YING (2015-7). "Prognostic significance of the BAALC gene expression in adult patients with acute myeloid leukemia: A meta-analysis". Molecular and Clinical Oncology. 3 (4): 880–888. doi:10.3892/mco.2015.562. ISSN 2049-9450. PMC 4486884. PMID 26171200.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c Xu, Bing (2012). "shRNA-Mediated BAALC knockdown affects proliferation and apoptosis in human acute myeloid leukemia cells". Hematology (Amsterdam, Netherlands). 17 (1): 35–40. doi:10.1179/102453312X13221316477499. PMID 22549446. S2CID 23319837. Retrieved November 15, 2017.
- ^ a b c Heuser, M (August 26, 2011). "Functional role of BAALC in leukemogenesis" (PDF). Leukemia. 26 (3): 532–536. doi:10.1038/leu.2011.228. PMID 21869843. S2CID 6215709. Retrieved November 15, 2017.
- ^ Zhou, Jing-dong; Yang, Lei; Zhang, Ying-ying; Yang, Jing; Wen, Xiang-mei; Guo, Hong; Yao, Dong-ming; Ma, Ji-chun; Chen, Qin (2015-01-01). "Overexpression of BAALC: clinical significance in Chinese de novo acute myeloid leukemia". Medical Oncology. 32 (1): 386. doi:10.1007/s12032-014-0386-9. ISSN 1357-0560. PMID 25428390. S2CID 207374620.
- ^ a b Weber, S.; Haferlach, T.; Alpermann, T.; Perglerová, K.; Schnittger, S.; Haferlach, C.; Kern, W. (2016). "CAS – Central Authentication Service". British Journal of Haematology. 175 (5): 904–916. doi:10.1111/bjh.14343. PMID 27662611. S2CID 10664675.
- ^ a b c d e Heesch, Svenja (June 10, 2010). "BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia" (PDF). Leukemia. 24 (8): 1429–1436. doi:10.1038/leu.2010.130. PMID 20535151. S2CID 10814244. Retrieved November 15, 2017.
- ^ "SWISS-MODEL | Q8WXS3". swissmodel.expasy.org. Retrieved 2017-11-30.