The role of viral infection in cancer was established
towards the beginning of 20th century. The ... more The role of viral infection in cancer was established towards the beginning of 20th century. The study of tumour viruses, their oncogenes and different mechanisms employed by these viruses to subvert the growth-suppressive and pro-apoptotic functions of host tumour suppressor genes has laid the foundation of cancer biology. The human tumour viruses induce malignancies after a prolonged latency and in conjunction with other environmental and host factors. The eight known human tumour viruses contribute to nearly 10–15% of the cancers worldwide. Advancements in research on virus-related cancers offer a plethora of opportunities to fight cancer by preventing viral spread through vaccination and use of antivirals. Besides, recent developments on viral oncogenic mechanisms should allow development of novel and targeted approaches for control and treatment of virus-associated human cancers.
The small ribosomal protein RPS27a is known to play a role in the activation of cellular checkpoi... more The small ribosomal protein RPS27a is known to play a role in the activation of cellular checkpoints via p53 which links ribosome biogenesis to cell cycle progression. Here, we show that RPS27a gene is a direct transcriptional target of p53 and is overexpressed in response to DNA damage. Elevated RPS27a level was associated with increased expression of p53 and its target p21(Waf1) gene. The RPS27a activity was specifically inhibited in the presence of a dominant negative mutant of p53. Down-regulation of ectopically expressed RPS27a by RNA interference blocked the activation of p21(waf1) in response to DNA damage. Thus, RPS27a appears to be a novel stress sensor in the cell which amplifies p53 response to arrest cell cycle.
Nucleolar assembly begins at the early G1 phase of the cell cycle and is a hub of ribosomal DNA t... more Nucleolar assembly begins at the early G1 phase of the cell cycle and is a hub of ribosomal DNA transcription and rRNA biosynthesis. The newlyformed rRNAs together with ribosomal proteins (RPs) constitute the building block of the ribosomal machinery. Although RPs play a major role in protein biosynthesis, their own regulation and expression is rather poorly understood. In the present study, we investigated the regulation of RP genes RPS27a, RPS24, RPS6, RPL9 and RPL4 in synchronized mammalian cell culture. Quantitative RT-PCR analysis indicated their expression during the mid to late G1 phase, whereas the rRNA genes were expressed during the early G1 phase of the cell cycle. The promoter reporter analysis of the RPS27a gene revealed that it could be synergistically stimulated by the transcription factors specificity protein 1 (Sp1) and cAMP response element-binding protein (CREB). However, E2F transcription factor 1 (E2F1) appeared to negatively regulate gene expression. Chromatin immunoprecipitation studies confirmed the promoter occupancy of Sp1, CREB and E2F1. Although Sp1 and CREB binding enhanced the promoter occupancy of histone acetyltransferases PCAF, p300 and CREB binding protein, E2F1 facilitated the recruitment of histone deacetylases. Both acetylation (histone H4 pan-acetyl, histone H3 acetyl Lys 14) and methylation (histone H3 trimethyl Lys 9) marks were observed in the RPS27a promoter region, suggesting their important regulatory role in gene expression. Because the promoter regions of most RP genes are well conserved, we propose that their orchestrated regulation and synthesis during the cell cycle facilitates ribosome biogenesis.
The role of viral infection in cancer was established
towards the beginning of 20th century. The ... more The role of viral infection in cancer was established towards the beginning of 20th century. The study of tumour viruses, their oncogenes and different mechanisms employed by these viruses to subvert the growth-suppressive and pro-apoptotic functions of host tumour suppressor genes has laid the foundation of cancer biology. The human tumour viruses induce malignancies after a prolonged latency and in conjunction with other environmental and host factors. The eight known human tumour viruses contribute to nearly 10–15% of the cancers worldwide. Advancements in research on virus-related cancers offer a plethora of opportunities to fight cancer by preventing viral spread through vaccination and use of antivirals. Besides, recent developments on viral oncogenic mechanisms should allow development of novel and targeted approaches for control and treatment of virus-associated human cancers.
The small ribosomal protein RPS27a is known to play a role in the activation of cellular checkpoi... more The small ribosomal protein RPS27a is known to play a role in the activation of cellular checkpoints via p53 which links ribosome biogenesis to cell cycle progression. Here, we show that RPS27a gene is a direct transcriptional target of p53 and is overexpressed in response to DNA damage. Elevated RPS27a level was associated with increased expression of p53 and its target p21(Waf1) gene. The RPS27a activity was specifically inhibited in the presence of a dominant negative mutant of p53. Down-regulation of ectopically expressed RPS27a by RNA interference blocked the activation of p21(waf1) in response to DNA damage. Thus, RPS27a appears to be a novel stress sensor in the cell which amplifies p53 response to arrest cell cycle.
Nucleolar assembly begins at the early G1 phase of the cell cycle and is a hub of ribosomal DNA t... more Nucleolar assembly begins at the early G1 phase of the cell cycle and is a hub of ribosomal DNA transcription and rRNA biosynthesis. The newlyformed rRNAs together with ribosomal proteins (RPs) constitute the building block of the ribosomal machinery. Although RPs play a major role in protein biosynthesis, their own regulation and expression is rather poorly understood. In the present study, we investigated the regulation of RP genes RPS27a, RPS24, RPS6, RPL9 and RPL4 in synchronized mammalian cell culture. Quantitative RT-PCR analysis indicated their expression during the mid to late G1 phase, whereas the rRNA genes were expressed during the early G1 phase of the cell cycle. The promoter reporter analysis of the RPS27a gene revealed that it could be synergistically stimulated by the transcription factors specificity protein 1 (Sp1) and cAMP response element-binding protein (CREB). However, E2F transcription factor 1 (E2F1) appeared to negatively regulate gene expression. Chromatin immunoprecipitation studies confirmed the promoter occupancy of Sp1, CREB and E2F1. Although Sp1 and CREB binding enhanced the promoter occupancy of histone acetyltransferases PCAF, p300 and CREB binding protein, E2F1 facilitated the recruitment of histone deacetylases. Both acetylation (histone H4 pan-acetyl, histone H3 acetyl Lys 14) and methylation (histone H3 trimethyl Lys 9) marks were observed in the RPS27a promoter region, suggesting their important regulatory role in gene expression. Because the promoter regions of most RP genes are well conserved, we propose that their orchestrated regulation and synthesis during the cell cycle facilitates ribosome biogenesis.
Uploads
Papers by Nagisa Nosrati
towards the beginning of 20th century. The study of
tumour viruses, their oncogenes and different mechanisms
employed by these viruses to subvert the
growth-suppressive and pro-apoptotic functions of
host tumour suppressor genes has laid the foundation
of cancer biology. The human tumour viruses induce
malignancies after a prolonged latency and in conjunction
with other environmental and host factors.
The eight known human tumour viruses contribute to
nearly 10–15% of the cancers worldwide. Advancements
in research on virus-related cancers offer a
plethora of opportunities to fight cancer by preventing
viral spread through vaccination and use of antivirals.
Besides, recent developments on viral oncogenic
mechanisms should allow development of novel and
targeted approaches for control and treatment of
virus-associated human cancers.
towards the beginning of 20th century. The study of
tumour viruses, their oncogenes and different mechanisms
employed by these viruses to subvert the
growth-suppressive and pro-apoptotic functions of
host tumour suppressor genes has laid the foundation
of cancer biology. The human tumour viruses induce
malignancies after a prolonged latency and in conjunction
with other environmental and host factors.
The eight known human tumour viruses contribute to
nearly 10–15% of the cancers worldwide. Advancements
in research on virus-related cancers offer a
plethora of opportunities to fight cancer by preventing
viral spread through vaccination and use of antivirals.
Besides, recent developments on viral oncogenic
mechanisms should allow development of novel and
targeted approaches for control and treatment of
virus-associated human cancers.