Sandbox Reserved 1485: Difference between revisions

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== Therapeutical perspective ==

KAP-1 can represent a good perspective for some therapies because it is implicate in the etablishment of viral latency, for example in the replication of Epstein-Barr Virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), Human cytomegalovirus (HCMV) and for endogenous retroviruses. Indeed, during the lytic infection, KAP-1 binds the viral genome and plays his role of repressor for the transcription of this genome (KAP-1 is activated when it is sumoylated and inactivate when it is phosphorylated). In this way, when KAP-1 is phosphorylated on serine 824 (by mTOR or ATM for example), it is not anymore able to recruit SETDB1 which is necessary to regulate the transcription. KAP-1 become thus inactive and the latency exits, and the viral genome will be transcribed and replicate. The result is so the switch from viral latency to the lytic cycle. The idea is then to use this characteristic of KAP-1 to develop a potential therapy able to purge the virus from infected individuals.

KAP-1 can represent a good perspective for some therapies because it is implicate in the etablishment of viral latency, for example in the replication of Epstein-Barr Virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), Human cytomegalovirus (HCMV) and for endogenous retroviruses. [6][7] Indeed, during the lytic infection, KAP-1 binds the viral genome and plays his role of repressor for the transcription of this genome (KAP-1 is activated when it is sumoylated and inactivate when it is phosphorylated). In this way, when KAP-1 is phosphorylated on serine 824 (by mTOR or ATM for example), it is not anymore able to recruit SETDB1 which is necessary to regulate the transcription. KAP-1 become thus inactive and the latency exits, and the viral genome will be transcribed and replicate. The result is so the switch from viral latency to the lytic cycle. The idea is then to use this characteristic of KAP-1 to develop a potential therapy able to purge the virus from infected individuals.[6][7][8]

</StructureSection>

Line 47:

[1] Eishou Matsuda, Yasutoshi Agata, Manabu Sugai, Tomoya Katakai, Hiroyuki Gonda, and Akira Shimizu, Targeting of Krüppel-associated Box-containing Zinc Finger Proteins to Centromeric Heterochromatin, IMPLICATION FOR THE GENE SILENCING MECHANISMS, Received for publication, November 27, 2000, and in revised form, January 18, 2001 Published, JBC Papers in Press, January 19, 2001.

[2] Lei Zeng, Kyoko L Yap, Alexey V Ivanov, Xueqi Wang, Shiraz Mujtaba, Olga Plotnikova, Frank J Rauscher III, and Ming-Ming Zhou, Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing, Published in final edited form as: ~~Nat~~ Struct Mol Biol. 2008 June ; 15(6): 626–633.

[2] Lei Zeng, Kyoko L Yap, Alexey V Ivanov, Xueqi Wang, Shiraz Mujtaba, Olga Plotnikova, Frank J Rauscher III, and Ming-Ming Zhou, Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing, Published in final edited form as:Nat Struct Mol Biol. 2008 June ; 15(6): 626–633.

[3] Sushma Iyengar and Peggy J. Farnham, KAP1 Protein: An Enigmatic Master Regulator of the Genome, Published, JBC Papers in Press, June 7, 2011, ~~DOI 10.1074/jbc.R111.252569~~

[3] Sushma Iyengar and Peggy J. Farnham, KAP1 Protein: An Enigmatic Master Regulator of the Genome, Published, JBC Papers in Press, June 7, 2011,

[4] Xu Li, Yung-Kang Lee, Jen-Chong Jeng, Yun Yen, David C. Schultz , Hsiu-Ming Shih, and David K. Ann, Role for KAP1 Serine 824 Phosphorylation and Sumoylation/Desumoylation Switch in Regulating KAP1-mediated Transcriptional Repression, Received for publication, August 20, 2007, and in revised form, October 9, 2007 Published, JBC Papers in Press, October 17, 2007.

[5] Yael Ziv, Dana Bielopolski, Yaron Galanty, Claudia Lukas, Yoichi Taya, David C. Schultz, Jiri Lukas, Simon Bekker-Jensen, Jiri Bartek and Yosef Shiloh, Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway, Received 22 March 2006; accepted 4 July 2006; published online 23 July 2006

[5] Yael Ziv, Dana Bielopolski, Yaron Galanty, Claudia Lukas, Yoichi Taya, David C. Schultz, Jiri Lukas, Simon Bekker-Jensen, Jiri Bartek and Yosef Shiloh, Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway, Received 22 March 2006; accepted 4 July 2006; published online 23 July 2006.

[6]

[6] Benjamin Rauwel, Suk Min Jang, Marco Cassano, Adamandia Kapopoulou, Isabelle Barde, Didier Trono , Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch, Elife, April 7, 2015.

[7]

[7] Helen M. Rowe, Johan Jakobsson, Daniel Mesnard, Jacques Rougemont, Séverine Reynard, Tugce Aktas, Pierre V. Maillard, Hillary Layard-Liesching, Sonia Verp, Julien Marquis, François Spitz, Daniel B. Constam & Didier Trono, KAP1 controls endogenous retroviruses in embryonic stem cells, Nature, January 14, 2010.

[8]

[8]Andreia Lee, Oya Cingöz, Yosef Sabo, Stephen P. Goff, Characterization of interaction between Trim28 and YY1 in silencing proviral DNA of Moloney murine leukemia virus, Received for publication, August 20, 2017, Revised 10 January 2018, Accepted 12 January 2018, Published, Virology , February 23, 2018.

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@@ Line 40: / Line 40: @@
 == Therapeutical perspective ==
-KAP-1 can represent a good perspective for some therapies because it is implicate in the etablishment of viral latency, for example in the replication of Epstein-Barr Virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), Human cytomegalovirus (HCMV) and for endogenous retroviruses. Indeed, during the lytic infection, KAP-1 binds the viral genome and plays his role of repressor for the transcription of this genome (KAP-1 is activated when it is sumoylated and inactivate when it is phosphorylated). In this way, when KAP-1 is phosphorylated on serine 824 (by mTOR or ATM for example), it is not anymore able to recruit SETDB1 which is necessary to regulate the transcription.  KAP-1 become thus inactive and the latency exits, and the viral genome will be transcribed and replicate. The result is so the switch from viral latency to the lytic cycle. The idea is then to use this characteristic of KAP-1 to develop a potential therapy able to purge the virus from infected individuals.
+KAP-1 can represent a good perspective for some therapies because it is implicate in the etablishment of viral latency, for example in the replication of Epstein-Barr Virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), Human cytomegalovirus (HCMV) and for endogenous retroviruses. [6][7] Indeed, during the lytic infection, KAP-1 binds the viral genome and plays his role of repressor for the transcription of this genome (KAP-1 is activated when it is sumoylated and inactivate when it is phosphorylated). In this way, when KAP-1 is phosphorylated on serine 824 (by mTOR or ATM for example), it is not anymore able to recruit SETDB1 which is necessary to regulate the transcription.  KAP-1 become thus inactive and the latency exits, and the viral genome will be transcribed and replicate. The result is so the switch from viral latency to the lytic cycle. The idea is then to use this characteristic of KAP-1 to develop a potential therapy able to purge the virus from infected individuals.[6][7][8]
 </StructureSection>
@@ Line 47: / Line 47: @@
 [1] Eishou Matsuda, Yasutoshi Agata, Manabu Sugai, Tomoya Katakai, Hiroyuki Gonda, and Akira Shimizu, Targeting of Krüppel-associated Box-containing Zinc Finger Proteins to Centromeric Heterochromatin, IMPLICATION FOR THE GENE SILENCING MECHANISMS, Received for publication, November 27, 2000, and in revised form, January 18, 2001 Published, JBC Papers in Press, January 19, 2001.
-[2] Lei Zeng, Kyoko L Yap, Alexey V Ivanov, Xueqi Wang, Shiraz Mujtaba, Olga Plotnikova, Frank J Rauscher III, and Ming-Ming Zhou, Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing, Published in final edited form as: Nat Struct Mol Biol. 2008 June ; 15(6): 626–633.
+[2] Lei Zeng, Kyoko L Yap, Alexey V Ivanov, Xueqi Wang, Shiraz Mujtaba, Olga Plotnikova, Frank J Rauscher III, and Ming-Ming Zhou, Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing, Published in final edited form as:Nat Struct Mol Biol. 2008 June ; 15(6): 626–633.
-[3] Sushma Iyengar and Peggy J. Farnham, KAP1 Protein: An Enigmatic Master Regulator of the Genome, Published, JBC Papers in Press, June 7, 2011, DOI 10.1074/jbc.R111.252569
+[3] Sushma Iyengar and Peggy J. Farnham, KAP1 Protein: An Enigmatic Master Regulator of the Genome, Published, JBC Papers in Press, June 7, 2011,
 [4] Xu Li, Yung-Kang Lee, Jen-Chong Jeng, Yun Yen, David C. Schultz , Hsiu-Ming Shih, and David K. Ann, Role for KAP1 Serine 824 Phosphorylation and Sumoylation/Desumoylation Switch in Regulating KAP1-mediated Transcriptional Repression, Received for publication, August 20, 2007, and in revised form, October 9, 2007 Published, JBC Papers in Press, October 17, 2007.
-[5] Yael Ziv, Dana Bielopolski, Yaron Galanty, Claudia Lukas, Yoichi Taya, David C. Schultz, Jiri Lukas, Simon Bekker-Jensen, Jiri Bartek and Yosef Shiloh, Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway, Received 22 March 2006; accepted 4 July 2006; published online 23 July 2006
+[5] Yael Ziv, Dana Bielopolski, Yaron Galanty, Claudia Lukas, Yoichi Taya, David C. Schultz, Jiri Lukas, Simon Bekker-Jensen, Jiri Bartek and Yosef Shiloh, Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway, Received 22 March 2006; accepted 4 July 2006; published online 23 July 2006.
-[6]
+[6] Benjamin Rauwel, Suk Min Jang, Marco Cassano, Adamandia Kapopoulou, Isabelle Barde, Didier Trono , Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch, Elife, April 7, 2015.
-[7]
+[7] Helen M. Rowe, Johan Jakobsson, Daniel Mesnard, Jacques Rougemont, Séverine Reynard, Tugce Aktas, Pierre V. Maillard, Hillary Layard-Liesching, Sonia Verp, Julien Marquis, François Spitz, Daniel B. Constam & Didier Trono, KAP1 controls endogenous retroviruses in embryonic stem cells, Nature, January 14, 2010.
-[8]
+[8]Andreia Lee, Oya Cingöz, Yosef Sabo, Stephen P. Goff, Characterization of interaction between Trim28 and YY1 in silencing proviral DNA of Moloney murine leukemia virus, Received for publication, August 20,  2017, Revised 10 January 2018, Accepted 12 January 2018, Published, Virology , February 23, 2018.