User:Andrea Foote/Sandbox 1: Difference between revisions
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*Serum response factor (SRF) | *Serum response factor (SRF) | ||
*Y-box-binding protein 1 (YB-1) (MSY1 in mice) | *Y-box-binding protein 1 (YB-1) (MSY1 in mice) | ||
*Retinoblastoma protein ( | *Retinoblastoma protein (Rb) | ||
*Rm62 RNA helicase of HIV | *Rm62 RNA helicase of HIV | ||
*Cdk2 moiety of cyclin A/Cdk2<ref>PMID:15707957</ref> | |||
== Disease == | == Disease == | ||
Mutations in the ''PURA'' gene resulting in haploinsufficiency are known to cause the neurological disease PURA syndrome, which has no cure. PURA syndrome appears early in development, with patients exhibiting severe developmental delay, seizures, feeding difficulty, intellectual disabilities, vision problems, hypotonia, and premature thelarche.<ref>PMID:29097605</ref> | Mutations in the ''PURA'' gene resulting in haploinsufficiency are known to cause the neurological disease PURA syndrome, which has no cure. PURA syndrome appears early in development, with patients exhibiting severe developmental delay, seizures, feeding difficulty, intellectual disabilities, vision problems, hypotonia, and premature thelarche.<ref>PMID:29097605</ref> Purα knock-out mice exhibit similar neurological symptoms such as severe tremor developing at about postnatal week two, and feeding difficulties. These mice die after approximately one month. Heterozygous mice display less severe symptoms including seizures upon handling. <ref>PMID:25342064</ref> Interestingly, to date there have been no published accounts of phenotypic abnormalities in humans or mice with mutations in Purβ. | ||
Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is another disease associated with abnormal activity of Purα. | Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is another disease associated with abnormal activity of Purα. In 2006, Johnson et al. observed that Purα colocalized with Fragile-X Mental Retardation Protein (FMRP) in mouse neuronal dendrites.<ref>PMID:16436378</ref> Purα also was found to be involved in dendritic mRNA transport, and in a ''Drosophila'' model of Fragile-X Tremor/Ataxia Syndrome it was hypothesized that the overexpression of FMR1 mRNA resulted in Purα being bound to these mRNAs leading to the apparent deficiency in Purα activity resulting in FXTAS symptoms.<ref>PMID:17698009</ref> | ||
== | == The Storybook Version of Pur Protein History (Just for Fun!) == | ||
In a lab across from central park in Manhattan, Edward Johnson and his postdoctoral fellow Andrew Bergemann stumbled on a protein in 1991 that would in years to come | In a lab across from central park in Manhattan, Edward Johnson and his postdoctoral fellow Andrew Bergemann stumbled on a protein in 1991 that would in years to come open doors to understanding diseases of neurological and cardiovascular origin. They named the protein Pur (pronounced “purr”) after its ability to bind a sequence of bent DNA rich in As and Gs, or purine nucleotides, called the “PUR element.” This region of DNA, found near the origin of replication, was thought to be involved in the regulation of DNA replication.<ref>PMID:1545807</ref> At the time, no sequence-specific single-stranded DNA binding proteins were known to exist. The novelty of the findings were tremendous, and paved the way for many future studies of sequence-specific DNA-binding proteins. | ||
While the focus of Johnson and Bergemann’s research was in DNA replication in cancer and AIDS, in the years that followed their discovery, Pur was found to interact with a tumor suppressor “retinoblastoma protein” or Rb. Likely as a result of funding available in cancer research and Rb, research has shifted from Pur’s role in DNA replication toward instead, its capacity to regulate transcription and translation, or the cellular processes involved in building proteins. | While the focus of Johnson and Bergemann’s research was in DNA replication in cancer and AIDS, in the years that followed their discovery, Pur was found to interact with a tumor suppressor “retinoblastoma protein” or Rb. Likely as a result of funding available in cancer research and Rb, research has shifted from Pur’s role in DNA replication toward instead, its capacity to regulate transcription and translation, or the cellular processes involved in building proteins. | ||
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In 1992, Bergemann, Johnson and Ma found what appeared to be a cousin of Pur. With only a C-terminal sequence to work from, the protein appeared to be similar but not identical to Pur. They named the putative protein “Purβ” and from then on referred to the original Pur protein as Purα.<ref>PMID:1448097</ref> Shortly thereafter in 1997, Kelm, et al. working to deduce the sequence of a protein they termed “vascular actin single-stranded DNA binding factor 2” (VACssBF2), isolated two different proteins of identical molecular weight to Purα and the putative Purβ. Upon sequencing and cloning of isolated cDNA, the team published the first full length sequence of what is now known to be Purβ.<ref>PMID:9334258</ref> Since this time, in humans three splice variants have been found of Purα, one of Purβ and two isoforms of another Pur family member Purγ: Purγ-A and Purγ-B. | In 1992, Bergemann, Johnson and Ma found what appeared to be a cousin of Pur. With only a C-terminal sequence to work from, the protein appeared to be similar but not identical to Pur. They named the putative protein “Purβ” and from then on referred to the original Pur protein as Purα.<ref>PMID:1448097</ref> Shortly thereafter in 1997, Kelm, et al. working to deduce the sequence of a protein they termed “vascular actin single-stranded DNA binding factor 2” (VACssBF2), isolated two different proteins of identical molecular weight to Purα and the putative Purβ. Upon sequencing and cloning of isolated cDNA, the team published the first full length sequence of what is now known to be Purβ.<ref>PMID:9334258</ref> Since this time, in humans three splice variants have been found of Purα, one of Purβ and two isoforms of another Pur family member Purγ: Purγ-A and Purγ-B. | ||
Purγ has been studied to a far lesser degree than Purα and Purβ. While little is yet known about the actions of the Purγ protein, Johnson and Liu in 2002 found that the Purγ-A isoform mRNA was expressed at very low levels or not at all in normal human tissues, but highly expressed in a panel of cancer cell types.<ref>PMID:12034829</ref> Similarly, Purγ-B mRNA was absent in human tissues except the testes, and in several tumor tissue types. | Purγ has been studied to a far lesser degree than Purα and Purβ. While little is yet known about the actions of the Purγ protein, Johnson and Liu in 2002 found that the Purγ-A isoform mRNA was expressed at very low levels or not at all in normal human tissues, but highly expressed in a panel of cancer cell types.<ref>PMID:12034829</ref> Similarly, Purγ-B mRNA was absent in human tissues except the testes, and in several tumor tissue types. Most of the research surrounding the Pur family of proteins has focused on Purα due to its involvement in neurological disorders, however interest in Purβ has increased in recent years as it has been implicated in cardiovascular disease, fibrosis and acute myelogenous leukemia.<ref>PMID:27064749</ref> | ||
== 3D Structures of Purα == | == 3D Structures of Purα == | ||
*[[ | *[[5fgp]] (I-II repeat complex with DNA. ''Drosophila m.'')<ref>PMID:19846792</ref> | ||
*[[ | *[[5fgo]] (III repeat dimer. ''Drosophila m.'')<ref>PMID:26744780</ref> | ||
*[[ | *[[3k44]] (I-II repeat, apo. ''Drosophila m.'')<ref>PMID:26744780</ref> | ||
*[[ | *[[3nm7]] (Apo. ''Borrelia b.'' Note: the ''Borrelia'' homolog of Purα contains only one PUR repeat)<ref>PMID:20976240</ref> | ||
*[[ | *[[3n8b]] (Apo. ''Borrelia b.'' Note: the ''Borrelia'' homolog of Purα contains only one PUR repeat)<ref>PMID:20976240</ref> | ||
== Additional Resources == | == Additional Resources == | ||