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Titel    Androgen Signaling
Herausgeber    SABiosciences
Jahr    2009
URL    https://web.archive.org/web/20090428134830/http://www.sabiosciences.com/pathway.php?sn=Androgen_Signaling

Literaturverz.   

no
Fußnoten    no
Fragmente    8


Fragmente der Quelle:
[1.] Rlm/Fragment 006 18 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:19:52 Hindemith
Fragment, Gesichtet, Rlm, SABiosciences Androgen Signaling 2009, SMWFragment, Schutzlevel sysop, Verschleierung

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The appropriate regulation of androgen activity is necessary for a range of developmental and physiological processes, particularly male sexual development and maturation. The appropriate regulation of androgen activity is necessary for a range of developmental and physiological processes, particularly male sexual development and maturation.
Anmerkungen

The source is not mentioned. To be continued on the following page.

Sichter
(SleepyHollow02), Hindemith

[2.] Rlm/Fragment 007 01 - Diskussion
Zuletzt bearbeitet: 2014-12-01 13:42:01 Singulus
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However, excessive production of adrenal androgens can cause premature puberty in young boys and their hypersecretion in females produce a masculine pattern of body hair and cessation of menstruation(6). Their miss-regulation [sic] is also implicated in the formation and progression of prostatic adenocarcinoma (7). Therefore, the removal of testicular androgens by castration has long been recognized to result in tumor regression, and surgical or pharmacological androgen ablation remains the predominant form of treatment for advanced prostate cancer. Androgen ablation therapy is often combined with the treatment of nonsteroidal antiandrogens, such as hydroxyflutamide, to block residual androgens action. Androgen Replacement Therapy has been in use for over 60 years to treat, with proven efficacy and safety, on patients with male hypogonadal disorders and/or failure of sexual development. Apart from that, the last decade has witnessed a wider therapeutic role of androgens for nonclassical indications.

6) Culig Z, Bartsch G 2006 Androgen axis in prostate cancer. J Cell Biochem 99:373–381

7) Bakin RE, Gioeli D, Sikes RA, Bissonette EA, Weber MJ 2003 Constitutive activation of the ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells. Cancer Res 63:1981–1989

16) Culig Z, Klocker H, Bartsch G, Steiner H, HobischA [sic] Anrogen [sic] Receptor in Prostate Cancer J Urol. 2003 Oct;170(4): 1363-1369.

17) Petre CE, Wetherill YB, Danielsen M, Knudsen KE. Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity. J Biol Chem 2002 Jan 18;277 (3):2207-15. Epub 2001 Nov 19.

However, excessive production of adrenal androgens can cause premature puberty in young boys and their hypersecretion in females, may produce a masculine pattern of body hair and cessation of menstruation (Ref.4). Their mis-regulation is also implicated in the formation and progression of prostatic adenocarcinoma (Ref.3). Therefore, the removal of testicular androgens by castration has long been recognized to result in tumor regression, and surgical or pharmacological androgen ablation remain the predominant form of treatment for advanced prostate cancer. Androgen ablation therapy is often combined with treatment with nonsteroidal antiandrogens, such as hydroxyflutamide, to block residual adrenal androgen action. Androgen Replacement Therapy has been in use for over 60 years to treat, with proven efficacy and safety, on patients with male hypogonadal disorders and/or failure of sexual development. Apart from that, the last decade has witnessed a wider therapeutic role of androgens for nonclassical indications.

3. Culig Z, Klocker H, Bartsch G, Steiner H, Hobisch A
Androgen Receptors in Prostate Cancer.
J Urol. 2003 Oct;170(4):1363-1369.

4. Petre CE, Wetherill YB, Danielsen M, Knudsen KE
Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity
J Biol Chem. 2002 Jan 18;277(3):2207-15. Epub 2001 Nov 19.

Anmerkungen

Not marked as a citation.

There is no reference (16) in the main text of Rlm's thesis.

Mark the difference in the placement of the year in the references (twice right behind the names, twice after the name of the journal) in Rlm demonstrated here, which is an indication of two different sources for these references. Furthermore it should be noted that this corresponds to the particular number of the journal being listed as well (in contrast to just the volume being identified).

Sichter
(Graf Isolan), SleepyHollow02

[3.] Rlm/Fragment 011 10 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:21:19 Hindemith
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The binding of androgens to AR induces dissociation of the AR from the HSPs proteins (Heat-Shock-Proteins) and subsequent receptor dimerization and translocation into the nucleus , facilitating the ability of AR to bind its cognate response elements, and recruit coregulators to promote the expression of target genes. The transcriptional activity of AR is greatly modulated by coregulatory proteins. Coactivators such as ARA70 ( Androgen Coactivators 70Kd) and ARA55 stabilize the process of ligand binding to AR. The ability of AR to be translocated into the nucleus is regulated by several coregulators such as the F-Actin binding protein Filamin. The binding of androgens to AR induces dissociation of the AR from the HSPs and subsequent receptor dimerization and translocation into the nucleus, facilitating the ability of AR to bind to its cognate response element, and recruit coregulators to promote the expression of target genes. The transcriptional activity of AR is greatly modulated by coregulatory proteins. Coactivators such as ARA70 (Androgen Receptor Coactivator, 70-Kd) and ARA55 stabilize the process of ligand binding to AR. The ability of AR to be translocated to the nucleus is regulated by several coregulators, for example, the F-Actin binding protein: Filamin.
Anmerkungen

The source is not given.

Sichter
(SleepyHollow02), Hindemith

[4.] Rlm/Fragment 012 01 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:26:02 Hindemith
Fragment, Gesichtet, Rlm, SABiosciences Androgen Signaling 2009, SMWFragment, Schutzlevel sysop, Verschleierung

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Inside the nucleus AR interacts with DNA by targeting specific nucleotide palindromic sequences termed Androgen Response Element (17). A number of coregulators themselves perform enzymatic activities such as phosphorylation or acetylation, modifying either the chromatin surrounding the promoter of the target gene or other coregulators. Among coactivators, the acetyltranferase , CBP (CREB Binding Protein) , the closely related p300 and other nuclear receptor coactivators p/CAF(p300/CBP Associated Factor), SRC1( Steroid Receptor Coactivator-1), and SRC3 (18).

17) Petre CE, Wetherill YB, Danielsen M, Knudsen KE. Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity. J Biol Chem 2002 Jan 18;277 (3):2207-15. Epub 2001 Nov 19.

18) Hao Yun Wong, Jan A. Burghoorn, Marije van Leeuwen, Petra E. De Ruiter, Esther Schippers, Leen J. Blok, Ka Wan LI, Henk L. Dekker, Luitzen De Jong, Jan Trapman, J. Anton Grotegoedand Albert O. Btinkmann. Phosphorylation of androgen receptor isoforms.Biochem J. 2004 Oct 15;383(Pt 2):267-76

Inside the nucleus, AR interacts with DNA by targeting specific nucleotide palindromic sequences termed ARE (Androgen Response Element) (Ref.2).

A number of coregulators themselves perform enzymatic activities such as phosphorylation or acetylation, modifying either the chromatin surrounding the promoter of the target gene or other coregulators. The prototypic coactivators of this type that possess acetyltransferase activity include, CBP (CREB Binding Protein), the closely related p300 and other nuclear receptor coactivators: p/CAF (p300/CBP Associated Factor), SRC1 (Steroid Receptor Coactivator-1), and SRC3 (Ref.3).


2. Lee DK, Chang C Molecular communication between androgen receptor and general transcription machinery. J Steroid Biochem Mol Biol. 2003 Jan;84(1):41-9.

3. Culig Z, Klocker H, Bartsch G, Steiner H, Hobisch A Androgen Receptors in Prostate Cancer. J Urol. 2003 Oct;170(4):1363-1369.

Anmerkungen

The source is not given.

Note that Petre et al. (2002) is the reference 4 in the source:

4. Petre CE, Wetherill YB, Danielsen M, Knudsen KE Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity. J Biol Chem. 2002 Jan 18;277(3):2207-15. Epub 2001 Nov 19.

Sichter
(SleepyHollow02), Hindemith

[5.] Rlm/Fragment 014 01 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:33:55 Hindemith
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PIAS (Protein Inhibitor of Activated Signal Transducer and Activator of Transcription STAT) family of proteins and ANPK ( Androgen Receptor-Interacting Nuclear Kinase) play major function. Transcriptional activation by AR ultimately requires the recruitment of RNA Pol II( RNA polymerase II) to the promoter of target genes. RNA Pol II recruitment is mediated through the assembly of GTFs (General Transcription Factor)to form the pre-initiation complex, the first step of which is the binding of TBP (TATA box-Binding Protein)near the transcriptional start site . TBP is part of multiprotein complex, the first step of which is the binding of TBP near the transcriptional start site. TBP is part of multiprotein complex which includes TFIID (Transcriptional Factor –IID) that induces DNA bending , bringing sequences upstream of the TATA element in closer proximity, and presumably enabling interaction between GTFs and steroid receptor-coregulators complexes. TFIIB binds directly to TBP and recruits the TFIIF-RNA Pol II complex. TFIIF interacts with TFIIB and RNA Pol II and has a role in transcription initiation and elongation. PIAS [Protein Inhibitor of Activated Signal Transducer and Activator of Transcription (STAT)] family of proteins and ANPK (Androgen Receptor-Interacting Nuclear Kinase) also interact with and coactivate AR. Transcriptional activation by AR ultimately requires the recruitment of RNA Pol II (RNA polymerase-II) to the promoter of target genes. RNA Pol II recruitment is mediated through the assembly of GTFs (General Transcription Factors) to form the preinitiation complex, the first step of which is the binding of TBP (TATA box-Binding Protein) near the transcriptional start site. TBP is part of a multiprotein complex, TFIID (Transcription Factor-IID), which also contains general and promoter-specific TAFII (TBP-Associated Factors) proteins. TBP binding induces DNA bending, bringing sequences upstream of the TATA element in closer proximity, presumably enabling interaction between GTFs and steroid receptor-coregulator complexes. TFIIB binds directly to TBP and functions to recruit the TFIIF-RNA Pol II complex. TFIIF domains, in addition to interacting with TFIIB and RNA Pol II, apparently also serve in transcription initiation and elongation.
Anmerkungen

The source is not given.

Sichter
(SleepyHollow02), Hindemith

[6.] Rlm/Fragment 015 01 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:37:12 Hindemith
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The ATPase/ Kinase TFIIE and helicase TFIIH are than recruited to RNA Pol II to facilitate DNA strand separation before transcription initiation. TFIIE and TFIIF are acetylated by p300 and p/CAF. Ubiquitin ligase activity has been identified for two AR coactivators, ARA54 and E6-AP.The coactivators with ubiquitin ligase activity contribute to nuclear receptor transactivation through targeting the degradation of corepressor. AR can also interact with a number of transcription factor including Activator Protein-1,SMAD3( Sma and Mad Related Family),NF-KappaB (Nuclear Factor-KappaB), SRY (Sex-determining Region-Y), and the Ets family of transcription factors.

Transcriptional corepression of androgen-bound AR can be attributed to three corepressors: cyclin D1, calreticulin and HBO1.Cyclin-D1 inhibits AR transactivation through a mechanism independent of its function in cell cycle regulation (7).

The calcium –binding protein calreticulinis [sic] localized to the endoplasmic reticulum and in the nucleus and has also been characterized as corepressor of AR.


7) Bakin RE, Gioeli D, Sikes RA, Bissonette EA, Weber MJ 2003 Constitutive activation of the ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells. Cancer Res 63:1981–1989

The ATPase and kinase TFIIE and the helicase TFIIH are then recruited to RNA Pol II to facilitate DNA strand separation before transcription initiation. TFIIE and TFIIF recruitment to RNA pol II are acetylated by p300 and p/CAF (Ref.2). Ubiquitin ligase activity has been identified for two AR coactivators, ARA54 and E6-AP. The coactivators with ubiquitin ligase activity contribute to nuclear receptor transcription through targeting the degradation of corepressors. AR can also interact with a number of transcription factors including Activator Protein-1, SMAD3 (Sma and Mad Related Family), NF-KappaB (Nuclear Factor-KappaB), SRY (Sex-determining Region-Y), and the Ets family of transcription factors.

Transcriptional corepression of androgen-bound AR can be attributed to three corepressors: cyclin-D1, calreticulin and HBO1. Cyclin-D1 inhibits AR transactivation through a mechanism independent of its function in cell cycle regulation (Ref.4). The calcium-binding protein calreticulin is localized to the endoplasmic reticulum and nucleus and has also been characterized as a corepressor of AR.


2. Lee DK, Chang C Molecular communication between androgen receptor and general transcription machinery. J Steroid Biochem Mol Biol. 2003 Jan;84(1):41-9.

4. Petre CE, Wetherill YB, Danielsen M, Knudsen KE Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity. J Biol Chem. 2002 Jan 18;277(3):2207-15. Epub 2001 Nov 19.

Anmerkungen

The source is not given.

Sichter
(SleepyHollow02), Hindemith

[7.] Rlm/Fragment 016 01 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:42:19 Hindemith
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The AR corepressor HBO1 is a member of MYST protein family that is characterized by a homologous zinc finger and carries an acetyltransferase domain. Although AR is normally thought to function as a homodimer, it has been found to heterodimerize with other nuclear receptors including the ER( Estrogen Receptor), GR ( Glucocorticoid Receptor) and TR4(Testicular Orphan Receptor 4) and in each case result in a decrease in AR transcriptional activity. In addition to the transcriptional or genomic mode of action by steroids, androgens, can also exert rapid, nongenomic effect. Nongenomic steroid activity typically involves the rapid induction of conventional second messenger signal transduction cascades. Nongenomic action of androgens can occur through multiple receptors. Androgens also stimulate an elevation in intracellular Ca2+ through GPCR(G-Protein Coupled Receptor) by activating an influx through nonvoltage-gated Ca2+ channels.The elevation of intracellular calcium activates signal transduction cascades, including PKA(Protein Kinase-A),PKC(Protein Kinase-C), and MAPKs( Mitogen Activated Protein Kinase), that can modulate the activity of the ARs and other transcription factors.

AR also interacts with intracellular tyrosine Kinase c-Src, triggering c-Src activation. One of the targets of c-Src is the adapter protein SHR [(SH2 Containing Protein), an upstream regulator of the MAPK pathway (18).]


18) Hao Yun Wong, Jan A. Burghoorn, Marije van Leeuwen, Petra E. De Ruiter, Esther Schippers, Leen J. Blok, Ka Wan LI, Henk L. Dekker, Luitzen De Jong, Jan Trapman, J. Anton Grotegoedand Albert O. Btinkmann. Phosphorylation of androgen receptor isoforms.Biochem J. 2004 Oct 15;383(Pt 2):267-76

The AR corepressor HBO1 is a member of the MYST protein family that is characterized by a homologous zinc finger and carries an acetyltransferase domain. Although AR is normally thought to function as a homodimer, it has been found to heterodimerize with other nuclear receptors including the ER (Estrogen Receptor), GR (Glucocorticoid Receptor) and TR4 (Testicular Orphan Receptor-4) and in each case result in a decrease in AR transcriptional activity.

In addition to the transcriptional or genomic mode of action by steroids, androgens, can also exert rapid, nongenomic effects. Nongenomic steroid activity typically involves the rapid induction of conventional second messenger signal transduction cascades. Nongenomic action of androgens can occur through multiple receptors. [...] Androgens also stimulate an elevation in intracellular Ca2+ through a GPCR (G-Protein Coupled Receptor) by activating an influx through nonvoltage-gated Ca2+ channels. The elevation of intracellular calcium activates signal transduction cascades, including PKA (Protein Kinase-A), PKC (Protein Kinase-C), and MAPKs (Mitogen-Activated Protein Kinase), that can modulate the activity of the ARs and other transcription factors. AR also interacts with the intracellular tyrosine kinase c-Src, triggering c-Src activation. One of the targets of c-Src is the adapter protein SHC (SH2 Containing Protein), an upstream regulator of the MAPK pathway.

Anmerkungen

The source is not given.

Sichter
(SleepyHollow02), Hindemith

[8.] Rlm/Fragment 017 01 - Diskussion
Zuletzt bearbeitet: 2014-12-10 23:44:23 Hindemith
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[One of the targets of c-Src is the adapter protein SHR] (SH2 Containing Protein), an upstream regulator of the MAPK pathway (18). AR phosphorylation by ERK2 is associated with enhanced AR transcriptional activity and an increased ability to recruit the coactivator ARA 70.The SRC family of transcriptional coactivators: SRC1, SRC3, and TIF2( Transcription Intermedary Factor -2) are targets of MAPK phosphoryation that result s in an increased ability of these coactivators to recruit additional coactivators complexes to the DNA-bound receptor. The non genomic rapid stimulation of the second messenger cascades by androgens may ultimately exert biological effects through modulation of the transcriptional activity of AR or other transcription factors. Such modulation may occur through direct phosphorylation of activators or their coregulators.

18) Hao Yun Wong, Jan A. Burghoorn, Marije van Leeuwen, Petra E. De Ruiter, Esther Schippers, Leen J. Blok, Ka Wan LI, Henk L. Dekker, Luitzen De Jong, Jan Trapman, J. Anton Grotegoedand Albert O. Btinkmann. Phosphorylation of androgen receptor isoforms.Biochem J. 2004 Oct 15;383(Pt 2):267-76

One of the targets of c-Src is the adapter protein SHC (SH2 Containing Protein), an upstream regulator of the MAPK pathway. [...] AR phosphorylation by ERK2 is associated with enhanced AR transcriptional activity and an increased ability to recruit the coactivator ARA70. The SRC family of transcriptional coactivators: SRC1, SRC3, and TIF2 (Transcription Intermediary Factor-2) are targets of MAPK phosphorylation that results in an increased ability of these coactivators to recruit additional coactivator complexes to the DNA-bound receptor. The nongenomic, rapid stimulation of second messenger cascades by androgens may ultimately exert biological effects through modulation of the transcriptional activity of AR or other transcription factors. Such modulation may occur through direct phosphorylation of transcriptional activators or their coregulators (Ref.1).

1. Heinlein CA, Chang C The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Mol Endocrinol. 2002 Oct;16(10):2181-7.

Anmerkungen

The source is not given.

Sichter
(SleepyHollow02), Hindemith

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