Sandbox Reserved 654: Difference between revisions

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'''p300/CBP-associated factor''' (PCAF), The human immunodeficiency virus type 1 (HIV-1) protein Tat is an atypical trans-activator of transcription which functions through binding to an RNA element known as the transactivation responsive region (TAR), located in the retroviral long-terminal repeat (LTR) [Cullen 1998], [Jeang et al. 1999] and [Karn 1999]. Tat binds to TAR RNA with high affinity but transiently [Keen et al. 1997] and [Rana and Jeang 1999]. Dissociation of Tat from TAR RNA facilitates Tat association with the assembled RNA polymerase II (RNAPII) complex [Deng et al. 2000] and [Kiernan et al. 1999]. The latter process enables the transcriptional machinery complex to elongate efficiently on the viral DNA template in order to produce full-length HIV transcripts during viral productive replication in infected cells [Adams et al. 1994] and [Garber and Jones 1999].<ref> sample ref </ref>

'''p300/CBP-associated factor''' (PCAF), <ref> sample ref </ref>

== '''Structure''' ==

Line 29:

== '''Mechanism''' ==

[[Image:Mechanism_figure.jpg |thumb|200 px|right| Recruitment of the components of a competent pre-initiation complex by Tat and cellular factors.]]

The human immunodeficiency virus type 1 (HIV-1) protein Tat is an atypical trans-activator of transcription which functions through binding to an RNA element known as the transactivation responsive region (TAR), located in the retroviral long-terminal repeat (LTR) [Cullen 1998], [Jeang et al. 1999] and [Karn 1999]. Tat binds to TAR RNA with high affinity but transiently [Keen et al. 1997] and [Rana and Jeang 1999]. Dissociation of Tat from TAR RNA facilitates Tat association with the assembled RNA polymerase II (RNAPII) complex [Deng et al. 2000] and [Kiernan et al. 1999]. The latter process enables the transcriptional machinery complex to elongate efficiently on the viral DNA template in order to produce full-length HIV transcripts during viral productive replication in infected cells [Adams et al. 1994] and [Garber and Jones 1999].The action of Tat has been well studied; however, the physiological mechanism through which Tat gains access to chromatin-associated LTRs is not understood.

There is an increasing body of evidence to suggest that Tat activity requires its association with several multiprotein complexes, which include histone acetyltransferase (HAT), p300/CBP (CREB binding protein), and p300/CBP-associated factor (PCAF)<ref> http://www.sciencedirect.com/science/article/pii/S1097276502004835 </ref> Tat acetylation at K50 results in its dissociation from TAR RNA and promotes formation of a multiprotein complex comprised of Tat, p300/CBP, and PCAF [Benkirane et al. 1998]. Furthermore, it has been shown that the HAT activity of PCAF is preferentially required for Tat transactivation of transcription of the integrated HIV-1 LTRs (Benkirane et al., 1998).

~~The action of Tat has been well studied; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood.~~

While the detailed molecular mechanisms underlying Tat dissociation from TAR RNA and its transactivation of transcription of the integrated HIV-1 genome remain elusive, increasing lines of evidence suggest that Tat activity requires its association with several multiprotein complexes, which include histone acetyltransferase (HAT) and p300/CBP-associated factor (PCAF)<ref> http://www.sciencedirect.com/science/article/pii/S1097276502004835 </ref> Tat acetylation at K50 results in its dissociation from TAR RNA and promotes formation of a multiprotein complex comprised of Tat, p300/CBP, and PCAF [Benkirane et al. 1998]. Furthermore, it has been shown that the HAT activity of PCAF is preferentially required for Tat transactivation of transcription of the integrated but not the unintegrated HIV-1 LTRs (Benkirane et al., 1998).

~~[[Image:Phenylalanine_Hydroxylase_mechanism.jpg |thumb|200 px|center|Reaction catalyzed by PheOH]]~~

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@@ Line 8: / Line 8: @@
 <Structure load='1JM4' size='500' frame='true' align='right' caption='This is a model of the pheylalanine hydroxylase dimer as found in humans. The green ball in within each subunit represents the iron ion in the catalytic domains.' scene='Insert optional scene name here' />
-'''p300/CBP-associated factor''' (PCAF), The human immunodeficiency virus type 1 (HIV-1) protein Tat is an atypical trans-activator of transcription which functions through binding to an RNA element known as the transactivation responsive region (TAR), located in the retroviral long-terminal repeat (LTR) [Cullen 1998], [Jeang et al. 1999] and [Karn 1999]. Tat binds to TAR RNA with high affinity but transiently [Keen et al. 1997] and [Rana and Jeang 1999]. Dissociation of Tat from TAR RNA facilitates Tat association with the assembled RNA polymerase II (RNAPII) complex [Deng et al. 2000] and [Kiernan et al. 1999]. The latter process enables the transcriptional machinery complex to elongate efficiently on the viral DNA template in order to produce full-length HIV transcripts during viral productive replication in infected cells [Adams et al. 1994] and [Garber and Jones 1999].<ref> sample ref </ref>
+'''p300/CBP-associated factor''' (PCAF), <ref> sample ref </ref>
 == '''Structure''' ==
@@ Line 29: / Line 29: @@
 == '''Mechanism''' ==
+[[Image:Mechanism_figure.jpg |thumb|200 px|right| Recruitment of the components of a competent pre-initiation complex by Tat and cellular factors.]]
+The human immunodeficiency virus type 1 (HIV-1) protein Tat is an atypical trans-activator of transcription which functions through binding to an RNA element known as the transactivation responsive region (TAR), located in the retroviral long-terminal repeat (LTR) [Cullen 1998], [Jeang et al. 1999] and [Karn 1999]. Tat binds to TAR RNA with high affinity but transiently [Keen et al. 1997] and [Rana and Jeang 1999]. Dissociation of Tat from TAR RNA facilitates Tat association with the assembled RNA polymerase II (RNAPII) complex [Deng et al. 2000] and [Kiernan et al. 1999]. The latter process enables the transcriptional machinery complex to elongate efficiently on the viral DNA template in order to produce full-length HIV transcripts during viral productive replication in infected cells [Adams et al. 1994] and [Garber and Jones 1999].The action of Tat has been well studied; however, the physiological mechanism through which Tat gains access to chromatin-associated LTRs is not understood.
+There is an increasing body of evidence to suggest that Tat activity requires its association with several multiprotein complexes, which include histone acetyltransferase (HAT), p300/CBP (CREB binding protein), and p300/CBP-associated factor (PCAF)<ref> http://www.sciencedirect.com/science/article/pii/S1097276502004835 </ref> Tat acetylation at K50 results in its dissociation from TAR RNA and promotes formation of a multiprotein complex comprised of Tat, p300/CBP, and PCAF [Benkirane et al. 1998]. Furthermore, it has been shown that the HAT activity of PCAF is preferentially required for Tat transactivation of transcription of the integrated HIV-1 LTRs (Benkirane et al., 1998).
-The action of Tat has been well studied; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood.
-While the detailed molecular mechanisms underlying Tat dissociation from TAR RNA and its transactivation of transcription of the integrated HIV-1 genome remain elusive, increasing lines of evidence suggest that Tat activity requires its association with several multiprotein complexes, which include histone acetyltransferase (HAT) and p300/CBP-associated factor (PCAF)<ref> http://www.sciencedirect.com/science/article/pii/S1097276502004835 </ref> Tat acetylation at K50 results in its dissociation from TAR RNA and promotes formation of a multiprotein complex comprised of Tat, p300/CBP, and PCAF [Benkirane et al. 1998]. Furthermore, it has been shown that the HAT activity of PCAF is preferentially required for Tat transactivation of transcription of the integrated but not the unintegrated HIV-1 LTRs (Benkirane et al., 1998).
-[[Image:Phenylalanine_Hydroxylase_mechanism.jpg |thumb|200 px|center|Reaction catalyzed by PheOH]]