Sandbox Reserved 1122: Difference between revisions

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==HUMAN BCL-2, ISOFORM1==

Human ~~BCL~~-2 (B-Cell Lymphoma 2), isoform 1 is an oncoprotein of 239 residues regulating cell death (apoptosis), notably acting as an anti-apoptotic. It is encoded by the ~~BCL2~~ gene located on the 18th chromosome (63.12-63.32 Mb). There are 2 isoforms of this protein (𝛼 and 𝛽), produced by alternative splicing, and which differ by 2 aminoacids (residues 96 (A→T) and 110 (R→G))<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC30598/ Solution structure of the antiapoptotic protein bcl-2]</ref>. Alteration of this protein is a caused of many cancers, and is also likely to be involved in schyzophrenia and autoimmunity.

Human Bcl-2 (B-Cell Lymphoma 2), isoform 1 is an oncoprotein of 239 residues regulating cell death (apoptosis), notably acting as an anti-apoptotic. It is encoded by the ''BCL-2'' gene located on the 18th chromosome (63.12-63.32 Mb). There are 2 isoforms of this protein (𝛼 and 𝛽), produced by alternative splicing, and which differ by 2 aminoacids (residues 96 (A→T) and 110 (R→G))<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC30598/ Solution structure of the antiapoptotic protein bcl-2]</ref>. Alteration of this protein is a caused of many cancers, and is also likely to be involved in schyzophrenia and autoimmunity.

== Structure ==

Human ~~BCL~~-2, isoform 1 is a 26kDa protein of 239 residues which is negatively charged at pH 7. The linear structure highlights 5 domains: <scene name='71/719863/Scenelucas/1'>BH4</scene> (10-30),

Human Bcl-2, isoform 1 is a 26kDa protein of 239 residues which is negatively charged at pH 7. The linear structure highlights 5 domains: <scene name='71/719863/Scenelucas/1'>BH4</scene> (10-30),

<scene name='71/719863/Scenebh3/2'>BH3</scene> (93-107), <scene name='71/719863/Scenebh1/1'>BH1</scene> (136-155), <scene name='71/719863/Scenebh2/1'>BH2</scene> (187-202) and a

transmembrane domain (212-233) (due to its poor behavior in solution, it has been replaced by a segment of Bcl-xl in the presented 3D structure). It organizes as eight alpha-helices: from 11 to 25 (1) , from 93 to 107 (2), from 109 to 118 (3), from 126 to 137 (4), from 144-163 (5), from 169 to 184 (6), from 186 to 191 (7) and from 194 to 202(8). Helices 5 and 6 are mostly hydrophobic and they are surrounded by four other helices characterized by their amphipathic properties. There are also 3 turns (32-34, 123-125, 138-140). The <scene name='71/719863/Bcl2helix/1'>3rd alpha-helix</scene> is a 3(10) helix, whereas ~~BCL~~-XL 3rd helix is a normal alpha-helix.

transmembrane domain (212-233) (due to its poor behavior in solution, it has been replaced by a segment of Bcl-xl in the presented 3D structure). It organizes as eight alpha-helices: from 11 to 25 (1) , from 93 to 107 (2), from 109 to 118 (3), from 126 to 137 (4), from 144-163 (5), from 169 to 184 (6), from 186 to 191 (7) and from 194 to 202(8). Helices 5 and 6 are mostly hydrophobic and they are surrounded by four other helices characterized by their amphipathic properties. There are also 3 turns (32-34, 123-125, 138-140). The <scene name='71/719863/Bcl2helix/1'>3rd alpha-helix</scene> is a 3(10) helix, whereas Bcl-Xl 3rd helix is a normal alpha-helix.

The transmembrane domain of Bcl-2 is made of 21 aminoacids and is located at the carboxy-terminal tail of the protein. It allows the docking of Bcl-2 in the mitochondrial outer membrane where the protein interacts with other effectors.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/24905660 Peptides derived from the transmembrane domain of Bcl-2 proteins as potential mitochondrial priming tools.]</ref>

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=== Cancer ===

~~BCL~~-2 is involved in many cancers such as breast, melanoma, prostate, chronic lymphocytic leukemia and lung cancers. In fact, its overexpression combined with an overexpression of c-Myc (another oncoprotein) produce aggressive B-lymphocytes. <ref>[http://www.bloodjournal.org/content/125/4/658 BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma]</ref>. It has also be shown that ~~BCL~~-2 overpexpression supresses DNA repair by enhancing Myc transcriptional activity.

Bcl-2 is involved in many cancers such as breast, melanoma, prostate, chronic lymphocytic leukemia and lung cancers. In fact, its overexpression combined with an overexpression of c-Myc (another oncoprotein) produce aggressive B-lymphocytes. <ref>[http://www.bloodjournal.org/content/125/4/658 BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma]</ref>. It has also be shown that Bcl-2 overpexpression supresses DNA repair by enhancing Myc transcriptional activity.

<ref>[http://www.jbc.org/content/281/20/14446.full ~~Bcl2~~ Suppresses DNA Repair by Enhancing c-Myc Transcriptional Activity]</ref> In fact, ~~BCL~~-2 is encoded by the BCL-2 gene (0,20 Mb) located on the 18th chromosome. Nevertheless, translocation between chromosome 14 and 18 juxtaposes the BCL-2 gene and the immunoglobulin locus. This brings the BCL-2 gene under the regulation of the immunoglobulin heavy-chain enhancer, diregulating BCL-2 expression level (involved in non-Hodgkin's lymphomas). <ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>

<ref>[http://www.jbc.org/content/281/20/14446.full Bcl-2 Suppresses DNA Repair by Enhancing c-Myc Transcriptional Activity]</ref> In fact, Bcl-2 is encoded by the ''BCL-2'' gene (0,20 Mb) located on the 18th chromosome. Nevertheless, translocation between chromosome 14 and 18 juxtaposes the ''BCL-2'' gene and the immunoglobulin locus. This brings the ''BCL-2'' gene under the regulation of the immunoglobulin heavy-chain enhancer, diregulating ''BCL-2'' expression level (involved in non-Hodgkin's lymphomas). <ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>

Other mechanisms appear to regulate and enhance the level of expression of BCL-2 : loss of endogenous microRNAs which normally repress ~~BCL~~-2 expression, and also hypomethylation.<ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>

Other mechanisms appear to regulate and enhance the level of expression of BCL-2 : loss of endogenous microRNAs which normally repress Bcl-2 expression, and also hypomethylation.<ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>

~~BCL~~-2 BH4 domain mediates the interaction with MBII domain of Myc. This interaction enhance c-Myc half-life, resulting in an enhancing of its total activity. c-Myc is a well known oncoprotein (transcription factor) involved in many cancers as it regulates a lot of genes of the cell cycle.

Bcl-2 <scene name='71/719863/Scenelucas/1'>BH4</scene> domain mediates the interaction with MBII domain of Myc. This interaction enhance c-Myc half-life, resulting in an enhancing of its total activity. c-Myc is a well known oncoprotein (transcription factor) involved in many cancers as it regulates a lot of genes of the cell cycle.

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@@ Line 2: / Line 2: @@
 ==HUMAN BCL-2, ISOFORM1==
 <StructureSection load='1g5m' size='400' side='right' caption='3D STRUCTURE OF HUMAN BCL-2, ISOFORM1 (from residue 3 to 207) BASED ON NMR SPECTROSCOPY' scene=''>
-Human BCL-2 (B-Cell Lymphoma 2), isoform 1 is an oncoprotein of 239 residues regulating cell death (apoptosis), notably acting as an anti-apoptotic. It is encoded by the BCL2 gene located on the 18th chromosome (63.12-63.32 Mb). There are 2 isoforms of this protein (𝛼 and 𝛽), produced by alternative splicing, and which differ by 2 aminoacids (residues 96 (A→T) and 110 (R→G))<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC30598/ Solution structure of the antiapoptotic protein bcl-2]</ref>. Alteration of this protein is a caused of many cancers, and is also likely to be involved in schyzophrenia and autoimmunity.
+Human Bcl-2 (B-Cell Lymphoma 2), isoform 1 is an oncoprotein of 239 residues regulating cell death (apoptosis), notably acting as an anti-apoptotic. It is encoded by the ''BCL-2'' gene located on the 18th chromosome (63.12-63.32 Mb). There are 2 isoforms of this protein (𝛼 and 𝛽), produced by alternative splicing, and which differ by 2 aminoacids (residues 96 (A→T) and 110 (R→G))<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC30598/ Solution structure of the antiapoptotic protein bcl-2]</ref>. Alteration of this protein is a caused of many cancers, and is also likely to be involved in schyzophrenia and autoimmunity.
 == Structure ==
-Human BCL-2, isoform 1 is a 26kDa protein of 239 residues which is negatively charged at pH 7. The linear structure highlights 5 domains: <scene name='71/719863/Scenelucas/1'>BH4</scene> (10-30),
+Human Bcl-2, isoform 1 is a 26kDa protein of 239 residues which is negatively charged at pH 7. The linear structure highlights 5 domains: <scene name='71/719863/Scenelucas/1'>BH4</scene> (10-30),
 <scene name='71/719863/Scenebh3/2'>BH3</scene> (93-107), <scene name='71/719863/Scenebh1/1'>BH1</scene> (136-155), <scene name='71/719863/Scenebh2/1'>BH2</scene> (187-202) and a
-transmembrane domain (212-233) (due to its poor behavior in solution, it has been replaced by a segment of Bcl-xl in the presented 3D structure). It organizes as eight alpha-helices: from 11 to 25 (1) , from 93 to 107 (2), from 109 to 118 (3), from 126 to 137 (4), from 144-163 (5), from 169 to 184 (6), from 186 to 191 (7) and from 194 to 202(8). Helices 5 and 6 are mostly hydrophobic and they are surrounded by four other helices characterized by their amphipathic properties. There are also 3 turns (32-34, 123-125, 138-140). The <scene name='71/719863/Bcl2helix/1'>3rd alpha-helix</scene> is a 3(10) helix, whereas BCL-XL 3rd helix is a normal alpha-helix.
+transmembrane domain (212-233) (due to its poor behavior in solution, it has been replaced by a segment of Bcl-xl in the presented 3D structure). It organizes as eight alpha-helices: from 11 to 25 (1) , from 93 to 107 (2), from 109 to 118 (3), from 126 to 137 (4), from 144-163 (5), from 169 to 184 (6), from 186 to 191 (7) and from 194 to 202(8). Helices 5 and 6 are mostly hydrophobic and they are surrounded by four other helices characterized by their amphipathic properties. There are also 3 turns (32-34, 123-125, 138-140). The <scene name='71/719863/Bcl2helix/1'>3rd alpha-helix</scene> is a 3(10) helix, whereas Bcl-Xl 3rd helix is a normal alpha-helix.
 The transmembrane domain of Bcl-2 is made of 21 aminoacids and is located at the carboxy-terminal tail of the protein. It allows the docking of Bcl-2 in the mitochondrial outer membrane where the protein interacts with other effectors.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/24905660 Peptides derived from the transmembrane domain of Bcl-2 proteins as potential mitochondrial priming tools.]</ref>
@@ Line 38: / Line 38: @@
 === Cancer ===
-BCL-2 is involved in many cancers such as breast, melanoma, prostate, chronic lymphocytic leukemia and lung cancers. In fact, its overexpression combined with an overexpression of c-Myc (another oncoprotein) produce aggressive B-lymphocytes. <ref>[http://www.bloodjournal.org/content/125/4/658 BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma]</ref>. It has also be shown that BCL-2 overpexpression supresses DNA repair by enhancing Myc transcriptional activity.
+Bcl-2 is involved in many cancers such as breast, melanoma, prostate, chronic lymphocytic leukemia and lung cancers. In fact, its overexpression combined with an overexpression of c-Myc (another oncoprotein) produce aggressive B-lymphocytes. <ref>[http://www.bloodjournal.org/content/125/4/658 BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma]</ref>. It has also be shown that Bcl-2 overpexpression supresses DNA repair by enhancing Myc transcriptional activity.
-<ref>[http://www.jbc.org/content/281/20/14446.full Bcl2 Suppresses DNA Repair by Enhancing c-Myc Transcriptional Activity]</ref> In fact, BCL-2 is encoded by the BCL-2 gene (0,20 Mb) located on the 18th chromosome. Nevertheless, translocation between chromosome 14 and 18 juxtaposes the BCL-2 gene and the immunoglobulin locus. This brings the BCL-2 gene under the regulation of the immunoglobulin heavy-chain enhancer, diregulating BCL-2 expression level (involved in non-Hodgkin's lymphomas). <ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>
+<ref>[http://www.jbc.org/content/281/20/14446.full Bcl-2 Suppresses DNA Repair by Enhancing c-Myc Transcriptional Activity]</ref> In fact, Bcl-2 is encoded by the ''BCL-2'' gene (0,20 Mb) located on the 18th chromosome. Nevertheless, translocation between chromosome 14 and 18 juxtaposes the ''BCL-2'' gene and the immunoglobulin locus. This brings the ''BCL-2'' gene under the regulation of the immunoglobulin heavy-chain enhancer, diregulating ''BCL-2'' expression level (involved in non-Hodgkin's lymphomas). <ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>
-Other mechanisms appear to regulate and enhance the level of expression of BCL-2 : loss of endogenous microRNAs which normally repress BCL-2 expression, and also hypomethylation.<ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>
+Other mechanisms appear to regulate and enhance the level of expression of BCL-2 : loss of endogenous microRNAs which normally repress Bcl-2 expression, and also hypomethylation.<ref>[http://www.nature.com/onc/journal/v27/n50/full/onc2008307a.html Bcl-2 family proteins and cancer]</ref>
-BCL-2 BH4 domain mediates the interaction with MBII domain of Myc. This interaction enhance c-Myc half-life, resulting in an enhancing of its total activity. c-Myc is a well known oncoprotein (transcription factor) involved in many cancers as it regulates a lot of genes of the cell cycle.
+Bcl-2 <scene name='71/719863/Scenelucas/1'>BH4</scene> domain mediates the interaction with MBII domain of Myc. This interaction enhance c-Myc half-life, resulting in an enhancing of its total activity. c-Myc is a well known oncoprotein (transcription factor) involved in many cancers as it regulates a lot of genes of the cell cycle.