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Wikipedia

LARP1

August 31, 2023

La-related protein 1 (LARP1) is a 150 kDa protein that in humans is encoded by the LARP1 gene.[5][6][7] LARP1 is a novel target of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a circuitry often hyperactivated in cancer which regulates cell growth and proliferation primarily through the regulation of protein synthesis.[8]

LARP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLARP1, LARP, La ribonucleoprotein domain family member 1, La ribonucleoprotein 1, translational regulator, Lar1, Lhp1
External IDsOMIM: 612059 MGI: 1890165 HomoloGene: 9089 GeneCards: LARP1
Orthologs
SpeciesHumanMouse
Entrez

23367

73158

Ensembl

ENSG00000155506

ENSMUSG00000037331

UniProt

Q6PKG0

Q6ZQ58

RefSeq (mRNA)

NM_028451

RefSeq (protein)

NP_082727

Location (UCSC)Chr 5: 154.68 – 154.82 MbChr 11: 57.9 – 57.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function Edit

LARP1 is the largest of a 7-member family of LARP proteins (others are: LARP1B, LARP3 (aka genuine La or SSB), LARP4A, LARP4B, LARP6 and LARP7).[9] All LARP proteins, including human LARPs, contain 2 conserved regions. The first conserved region shares homology with La proteins (called the La motif, see SSB) whereas the second conserved region (called the LA- motif) is restricted to LARP proteins. LARP1 and 1B also contain a conserved "DM15 region" within their C-terminus.[10] This region is unique and has been shown to be required for RNA-binding. Mouse Larp1 is expressed in dorsal root ganglia and spinal cord, as well as in developing organs characterized by epithelial-mesenchymal interactions.[6] Human LARP1 is present at low levels in normal, non-embryonic cells but is highly expressed in epithelial cancers (such as ovarian, colorectal, prostate, non-small cell lung, hepatocellular and cervical cancers).[11][12][13][14] Some studies have shown that high levels of LARP1 protein correlate with worse prognosis in cancer patients.[15][16]

LARP1 binds to and regulates the translation of terminal oligopyrimidine motif (TOP mRNAs) and can directly interact with the 5' cap of mRNAs.[17][18] It has also been shown to interact with the 3' end and coding regions (CDS) of other genes.[17] LARP1 protein colocalizes with stress granules and P-bodies,[19] which function in RNA storage and degradation. It has been suggested that LARP1 functions in P-bodies to attenuate the abundance of conserved Ras-MAPK mRNAs. The cluster of LARP1 homologs may function to control the expression of key developmental regulators.[19]

Several studies have demonstrated that LARP1 deficiency selectively affects the recruitment of TOP mRNAs to polysomes[citation needed]. In some cancer cells, LARP1 deficiency reduces proliferation and activates apoptotic cell death.[13] Even though a decrease abundance of proteins encoded by TOP mRNAs has been reported in LARP1 silenced cells, some researchers believe that this can be explained simply by the reduced number of TOP mRNA transcripts in LARP1-deficient cells[citation needed].

References Edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000155506 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037331 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (October 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
  6. ^ a b Chauvet S, Maurel-Zaffran C, Miassod R, Jullien N, Pradel J, Aragnol D (July 2000). "dlarp, a new candidate Hox target in Drosophila whose orthologue in mouse is expressed at sites of epithelium/mesenchymal interactions". Developmental Dynamics. 218 (3): 401–13. doi:10.1002/1097-0177(200007)218:3<401::AID-DVDY1009>3.0.CO;2-6. PMID 10878606.
  7. ^ "Entrez Gene: LARP1 La ribonucleoprotein domain family, member 1".
  8. ^ Tcherkezian J, Cargnello M, Romeo Y, Huttlin EL, Lavoie G, Gygi SP, Roux PP (Feb 2014). "Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5'TOP mRNA translation". Genes Dev. 28 (4): 357–71. doi:10.1101/gad.231407.113. PMC 3937514. PMID 24532714.
  9. ^ Bousquet-Antonelli C, Deragon JM (May 2009). "A comprehensive analysis of the La-motif protein superfamily". RNA. 15 (5): 750–64. doi:10.1261/rna.1478709. PMC 2673062. PMID 19299548.
  10. ^ Lahr RM, Mack SM, Héroux A, Blagden SP, Bousquet-Antonelli C, Deragon JM, Berman AJ (September 2015). "The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence". Nucleic Acids Research. 43 (16): 8077–88. doi:10.1093/nar/gkv748. PMC 4652764. PMID 26206669.
  11. ^ Stavraka C, Blagden S (October 2015). "The La-Related Proteins, a Family with Connections to Cancer". Biomolecules. 5 (4): 2701–22. doi:10.3390/biom5042701. PMC 4693254. PMID 26501340.
  12. ^ Mura M, Hopkins TG, Michael T, Abd-Latip N, Weir J, Aboagye E, Mauri F, Jameson C, Sturge J, Gabra H, Bushell M, Willis AE, Curry E, Blagden SP (September 2015). "LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression". Oncogene. 34 (39): 5025–36. doi:10.1038/onc.2014.428. PMC 4430325. PMID 25531318.
  13. ^ a b Hopkins TG, Mura M, Al-Ashtal HA, Lahr RM, Abd-Latip N, Sweeney K, et al. (February 2016). "The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer". Nucleic Acids Research. 44 (3): 1227–46. doi:10.1093/nar/gkv1515. PMC 4756840. PMID 26717985.
  14. ^ Xie C, Huang L, Xie S, Xie D, Zhang G, Wang P, Peng L, Gao Z (October 2013). "LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma". Journal of Translational Medicine. 11: 272. doi:10.1186/1479-5876-11-272. PMC 3814951. PMID 24159927.
  15. ^ Ye L, Lin ST, Mi YS, Liu Y, Ma Y, Sun HM, Peng ZH, Fan JW (November 2016). "Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target". Tumour Biology. 37 (11): 14585–14594. doi:10.1007/s13277-016-5332-3. PMC 5126195. PMID 27614686.
  16. ^ Xu Z, Xu J, Lu H, Lin B, Cai S, Guo J, Zang F, Chen R (December 2017). "LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non-small cell lung carcinoma". Oncology Reports. 38 (6): 3659–3667. doi:10.3892/or.2017.6040. PMID 29039571.
  17. ^ a b Hong S, Freeberg MA, Han T, Kamath A, Yao Y, Fukuda T, Suzuki T, Kim JK, Inoki K (June 2017). "LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs". eLife. 6. doi:10.7554/elife.25237. PMC 5484620. PMID 28650797.
  18. ^ Lahr RM, Fonseca BD, Ciotti GE, Al-Ashtal HA, Jia JJ, Niklaus MR, Blagden SP, Alain T, Berman AJ (April 2017). "La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs". eLife. 6. doi:10.7554/elife.24146. PMC 5419741. PMID 28379136.
  19. ^ a b Nykamp K, Lee MH, Kimble J (July 2008). "C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis". RNA. 14 (7): 1378–89. doi:10.1261/rna.1066008. PMC 2441978. PMID 18515547.

Further reading Edit

  • Horke S, Reumann K, Schweizer M, Will H, Heise T (June 2004). "Nuclear trafficking of La protein depends on a newly identified nucleolar localization signal and the ability to bind RNA". The Journal of Biological Chemistry. 279 (25): 26563–70. doi:10.1074/jbc.M401017200. PMID 15060081.
  • Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
  • Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (August 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660. S2CID 2371325.
  • Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
  • Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.


 

This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it.

August 31, 2023
larp1, related, protein, protein, that, humans, encoded, gene, novel, target, mammalian, target, rapamycin, complex, mtorc1, signaling, pathway, circuitry, often, hyperactivated, cancer, which, regulates, cell, growth, proliferation, primarily, through, regula. La related protein 1 LARP1 is a 150 kDa protein that in humans is encoded by the LARP1 gene 5 6 7 LARP1 is a novel target of the mammalian target of rapamycin complex 1 mTORC1 signaling pathway a circuitry often hyperactivated in cancer which regulates cell growth and proliferation primarily through the regulation of protein synthesis 8 LARP1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4ZC4 5C0VIdentifiersAliasesLARP1 LARP La ribonucleoprotein domain family member 1 La ribonucleoprotein 1 translational regulator Lar1 Lhp1External IDsOMIM 612059 MGI 1890165 HomoloGene 9089 GeneCards LARP1Gene location Human Chr Chromosome 5 human 1 Band5q33 2Start154 682 986 bp 1 End154 817 605 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 11 B1 3Start57 899 890 bp 2 End57 952 860 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insuperior vestibular nucleusspinal gangliamiddle temporal gyrustrigeminal ganglionpylorusBrodmann area 23renal medullaponssuperior surface of tonguenippleTop expressed inprimitive streakcrypt of lieberkuhn of small intestinelacrimal glandtrigeminal ganglionleft lobe of liverentorhinal cortexsomiteankleknee jointvastus lateralis muscleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionRNA cap binding translation activator activity translation initiation factor binding protein binding eukaryotic initiation factor 4E binding mRNA 3 UTR binding mRNA 5 UTR binding RNA binding cadherin binding RNA 7 methylguanosine cap binding ribosomal small subunit bindingCellular componentcytoplasm TORC1 complex membrane polysome cytoplasmic stress granule polysomal ribosomeBiological processtranslational initiation positive regulation of macroautophagy positive regulation of viral genome replication cell population proliferation TOR signaling protein biosynthesis positive regulation of translation negative regulation of translation TORC1 signaling mRNA stabilization cellular response to rapamycin response to amino acid starvation regulation of translation negative regulation of translational initiationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez2336773158EnsemblENSG00000155506ENSMUSG00000037331UniProtQ6PKG0Q6ZQ58RefSeq mRNA NM 015315NM 033551NM 001367713NM 001367714NM 001367715NM 001367716NM 001367717NM 001367718NM 001367719NM 028451RefSeq protein NP 056130NP 001354642NP 001354643NP 001354644NP 001354645NP 001354646NP 001354647NP 001354648NP 291029NP 082727Location UCSC Chr 5 154 68 154 82 MbChr 11 57 9 57 95 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseFunction EditLARP1 is the largest of a 7 member family of LARP proteins others are LARP1B LARP3 aka genuine La or SSB LARP4A LARP4B LARP6 and LARP7 9 All LARP proteins including human LARPs contain 2 conserved regions The first conserved region shares homology with La proteins called the La motif see SSB whereas the second conserved region called the LA motif is restricted to LARP proteins LARP1 and 1B also contain a conserved DM15 region within their C terminus 10 This region is unique and has been shown to be required for RNA binding Mouse Larp1 is expressed in dorsal root ganglia and spinal cord as well as in developing organs characterized by epithelial mesenchymal interactions 6 Human LARP1 is present at low levels in normal non embryonic cells but is highly expressed in epithelial cancers such as ovarian colorectal prostate non small cell lung hepatocellular and cervical cancers 11 12 13 14 Some studies have shown that high levels of LARP1 protein correlate with worse prognosis in cancer patients 15 16 LARP1 binds to and regulates the translation of terminal oligopyrimidine motif TOP mRNAs and can directly interact with the 5 cap of mRNAs 17 18 It has also been shown to interact with the 3 end and coding regions CDS of other genes 17 LARP1 protein colocalizes with stress granules and P bodies 19 which function in RNA storage and degradation It has been suggested that LARP1 functions in P bodies to attenuate the abundance of conserved Ras MAPK mRNAs The cluster of LARP1 homologs may function to control the expression of key developmental regulators 19 Several studies have demonstrated that LARP1 deficiency selectively affects the recruitment of TOP mRNAs to polysomes citation needed In some cancer cells LARP1 deficiency reduces proliferation and activates apoptotic cell death 13 Even though a decrease abundance of proteins encoded by TOP mRNAs has been reported in LARP1 silenced cells some researchers believe that this can be explained simply by the reduced number of TOP mRNA transcripts in LARP1 deficient cells citation needed References Edit a b c GRCh38 Ensembl release 89 ENSG00000155506 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000037331 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Nagase T Ishikawa K Suyama M Kikuno R Miyajima N Tanaka A Kotani H Nomura N Ohara O October 1998 Prediction of the coding sequences of unidentified human genes XI The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro DNA Research 5 5 277 86 doi 10 1093 dnares 5 5 277 PMID 9872452 a b Chauvet S Maurel Zaffran C Miassod R Jullien N Pradel J Aragnol D July 2000 dlarp a new candidate Hox target in Drosophila whose orthologue in mouse is expressed at sites of epithelium mesenchymal interactions Developmental Dynamics 218 3 401 13 doi 10 1002 1097 0177 200007 218 3 lt 401 AID DVDY1009 gt 3 0 CO 2 6 PMID 10878606 Entrez Gene LARP1 La ribonucleoprotein domain family member 1 Tcherkezian J Cargnello M Romeo Y Huttlin EL Lavoie G Gygi SP Roux PP Feb 2014 Proteomic analysis of cap dependent translation identifies LARP1 as a key regulator of 5 TOP mRNA translation Genes Dev 28 4 357 71 doi 10 1101 gad 231407 113 PMC 3937514 PMID 24532714 Bousquet Antonelli C Deragon JM May 2009 A comprehensive analysis of the La motif protein superfamily RNA 15 5 750 64 doi 10 1261 rna 1478709 PMC 2673062 PMID 19299548 Lahr RM Mack SM Heroux A Blagden SP Bousquet Antonelli C Deragon JM Berman AJ September 2015 The La related protein 1 specific domain repurposes HEAT like repeats to directly bind a 5 TOP sequence Nucleic Acids Research 43 16 8077 88 doi 10 1093 nar gkv748 PMC 4652764 PMID 26206669 Stavraka C Blagden S October 2015 The La Related Proteins a Family with Connections to Cancer Biomolecules 5 4 2701 22 doi 10 3390 biom5042701 PMC 4693254 PMID 26501340 Mura M Hopkins TG Michael T Abd Latip N Weir J Aboagye E Mauri F Jameson C Sturge J Gabra H Bushell M Willis AE Curry E Blagden SP September 2015 LARP1 post transcriptionally regulates mTOR and contributes to cancer progression Oncogene 34 39 5025 36 doi 10 1038 onc 2014 428 PMC 4430325 PMID 25531318 a b Hopkins TG Mura M Al Ashtal HA Lahr RM Abd Latip N Sweeney K et al February 2016 The RNA binding protein LARP1 is a post transcriptional regulator of survival and tumorigenesis in ovarian cancer Nucleic Acids Research 44 3 1227 46 doi 10 1093 nar gkv1515 PMC 4756840 PMID 26717985 Xie C Huang L Xie S Xie D Zhang G Wang P Peng L Gao Z October 2013 LARP1 predict the prognosis for early stage and AFP normal hepatocellular carcinoma Journal of Translational Medicine 11 272 doi 10 1186 1479 5876 11 272 PMC 3814951 PMID 24159927 Ye L Lin ST Mi YS Liu Y Ma Y Sun HM Peng ZH Fan JW November 2016 Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target Tumour Biology 37 11 14585 14594 doi 10 1007 s13277 016 5332 3 PMC 5126195 PMID 27614686 Xu Z Xu J Lu H Lin B Cai S Guo J Zang F Chen R December 2017 LARP1 is regulated by the XIST miR 374a axis and functions as an oncogene in non small cell lung carcinoma Oncology Reports 38 6 3659 3667 doi 10 3892 or 2017 6040 PMID 29039571 a b Hong S Freeberg MA Han T Kamath A Yao Y Fukuda T Suzuki T Kim JK Inoki K June 2017 LARP1 functions as a molecular switch for mTORC1 mediated translation of an essential class of mRNAs eLife 6 doi 10 7554 elife 25237 PMC 5484620 PMID 28650797 Lahr RM Fonseca BD Ciotti GE Al Ashtal HA Jia JJ Niklaus MR Blagden SP Alain T Berman AJ April 2017 La related protein 1 LARP1 binds the mRNA cap blocking eIF4F assembly on TOP mRNAs eLife 6 doi 10 7554 elife 24146 PMC 5419741 PMID 28379136 a b Nykamp K Lee MH Kimble J July 2008 C elegans La related protein LARP 1 localizes to germline P bodies and attenuates Ras MAPK signaling during oogenesis RNA 14 7 1378 89 doi 10 1261 rna 1066008 PMC 2441978 PMID 18515547 Further reading EditHorke S Reumann K Schweizer M Will H Heise T June 2004 Nuclear trafficking of La protein depends on a newly identified nucleolar localization signal and the ability to bind RNA The Journal of Biological Chemistry 279 25 26563 70 doi 10 1074 jbc M401017200 PMID 15060081 Beausoleil SA Jedrychowski M Schwartz D Elias JE Villen J Li J Cohn MA Cantley LC Gygi SP August 2004 Large scale characterization of HeLa cell nuclear phosphoproteins Proceedings of the National Academy of Sciences of the United States of America 101 33 12130 5 Bibcode 2004PNAS 10112130B doi 10 1073 pnas 0404720101 PMC 514446 PMID 15302935 Jin J Smith FD Stark C Wells CD Fawcett JP Kulkarni S Metalnikov P O Donnell P Taylor P Taylor L Zougman A Woodgett JR Langeberg LK Scott JD Pawson T August 2004 Proteomic functional and domain based analysis of in vivo 14 3 3 binding proteins involved in cytoskeletal regulation and cellular organization Current Biology 14 16 1436 50 doi 10 1016 j cub 2004 07 051 PMID 15324660 S2CID 2371325 Beausoleil SA Villen J Gerber SA Rush J Gygi SP October 2006 A probability based approach for high throughput protein phosphorylation analysis and site localization Nature Biotechnology 24 10 1285 92 doi 10 1038 nbt1240 PMID 16964243 S2CID 14294292 Olsen JV Blagoev B Gnad F Macek B Kumar C Mortensen P Mann M November 2006 Global in vivo and site specific phosphorylation dynamics in signaling networks Cell 127 3 635 48 doi 10 1016 j cell 2006 09 026 PMID 17081983 S2CID 7827573 nbsp This article on a gene on human chromosome 5 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title LARP1 amp oldid 1136204489, wikipedia, wiki, book, books, library,

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