RGD Reference Report - Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus. - Rat Genome Database

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Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus.

Authors: Shakib, K  Norman, JT  Fine, LG  Brown, LR  Godovac-Zimmermann, J 
Citation: Shakib K, etal., Proteomics. 2005 Jul;5(11):2819-38.
RGD ID: 1598733
Pubmed: PMID:15942958   (View Abstract at PubMed)
DOI: DOI:10.1002/pmic.200401108   (Journal Full-text)

Proteomics methods were used to characterize proteins that change their form or abundance in the nucleus of NRK49F rat kidney fibroblasts during prolonged hypoxia (1% O(2), 12 h). Of the 791 proteins that were monitored, about 20% showed detectable changes. The 51 most abundant proteins were identified by mass spectrometry. Changes in nuclear receptor transcription factors (THRalpha1, RORalpha4, HNF4alpha, NUR77), other transcription factors (GATA1, AP-2alpha, OCT1, ATF6alpha, ZFP161, ZNF354A, PDCD2), and transcription cofactors (PC4, PCAF, MTA1, TCEA1, JMY) are indicative of major, co-ordinated changes in transcription. Proteins involved in DNA repair/recombination, ribosomal RNA synthesis, RNA processing, nuclear transport, nuclear organization, protein translation, glycolysis, lipid metabolism, several protein kinases (PKCdelta, MAP3K4, GRK3), as well as proteins with no established functional role were also observed. The observed proteins suggest nuclear regulatory roles for proteins involved in cytosolic processes such as glycolysis and fatty acid metabolism, and roles in overall nuclear structure/organization for proteins previously associated with meiosis and/or spermatogenesis (synaptonemal complex proteins 1 and 2 (SYCP1, SYCP2), meiosis-specific nuclear structural protein 1 (MNS1), LMNC2, zinc finger protein 99 (ZFP99)). Proteins associated with cytoplasmic membrane functions (ACTN4, hyaluronan mediated motility receptor (RHAMM), VLDLR, GRK3) and/or endocytosis (DNM2) were also seen. For 30% of the identified proteins, new isoforms indicative of alternative transcription were detected (e.g., GATA1, ATF6alpha, MTA1, MLH1, MYO1C, UBF, SYCP2, EIF3S10, MAP3K4, ZFP99). Comparison with proteins involved in cell death, cancer, and testis/meiosis/spermatogenesis suggests commonalities, which may reflect fundamental mechanisms for down-regulation of cellular function.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Acsl6Ratresponse to hypoxia  IEP  RGD 
Actn4Ratresponse to hypoxia  IEP  RGD 
Mlh1Ratresponse to hypoxia  IEP  RGD 
VldlrRatresponse to hypoxia  IEP  RGD 
Zfp354aRatresponse to hypoxia  IEP  RGD 


Genes (Rattus norvegicus)
Acsl6  (acyl-CoA synthetase long-chain family member 6) Actn4  (actinin alpha 4) Mlh1  (mutL homolog 1)
Vldlr  (very low density lipoprotein receptor) Zfp354a  (zinc finger protein 354A)

Gene Atf6 activating transcription factor 6 Rattus norvegicus
Gene Cebpz CCAAT/enhancer binding protein zeta Rattus norvegicus
Gene Dnm2 dynamin 2 Rattus norvegicus
Gene Eef1a1 eukaryotic translation elongation factor 1 alpha 1 Rattus norvegicus
Gene Eif3a eukaryotic translation initiation factor 3, subunit A Rattus norvegicus
Gene G6pd glucose-6-phosphate dehydrogenase Rattus norvegicus
Gene Gapdh glyceraldehyde-3-phosphate dehydrogenase Rattus norvegicus
Gene Gata1 GATA binding protein 1 Rattus norvegicus
Gene Grk3 G protein-coupled receptor kinase 3 Rattus norvegicus
Gene Gstp1 glutathione S-transferase pi 1 Rattus norvegicus
Gene Hnf4a hepatocyte nuclear factor 4, alpha Rattus norvegicus
Gene Hnrnph1 heterogeneous nuclear ribonucleoprotein H1 Rattus norvegicus
Gene Kat2b lysine acetyltransferase 2B Rattus norvegicus
Gene Lig1 DNA ligase 1 Rattus norvegicus
Gene Lmna lamin A/C Rattus norvegicus
Gene Mta1 metastasis associated 1 Rattus norvegicus
Gene Myo1c myosin 1C Rattus norvegicus
Gene Nr4a1 nuclear receptor subfamily 4, group A, member 1 Rattus norvegicus
Gene Pdcd2 programmed cell death 2 Rattus norvegicus
Gene Pgam1 phosphoglycerate mutase 1 Rattus norvegicus
Gene Pou2f1 POU class 2 homeobox 1 Rattus norvegicus
Gene Ran RAN, member RAS oncogene family Rattus norvegicus
Gene Sub1 SUB1 regulator of transcription Rattus norvegicus
Gene Sycp1 synaptonemal complex protein 1 Rattus norvegicus
Gene Sycp2 synaptonemal complex protein 2 Rattus norvegicus
Gene Tfap2a transcription factor AP-2 alpha Rattus norvegicus
Gene Tpi1 triosephosphate isomerase 1 Rattus norvegicus
Gene Ubtf upstream binding transcription factor Rattus norvegicus
Gene Zbtb14 zinc finger and BTB domain containing 14 Rattus norvegicus
Gene Zranb2 zinc finger RANBP2-type containing 2 Rattus norvegicus