title: Enzyme dimension of the ribosomal protein S4 across plant and animal kingdoms.
abstract: BACKGROUND
  The protein S4 of the smaller ribosomal subunit is centrally important for its anchorage role in ribosome assembly and rRNA binding. Eubacterial S4 also facilitates synthesis of rRNA, and restrains translation of ribosomal proteins of the same polycistronic mRNA. Eukaryotic S4 has no homolog in eubacterial kingdom, nor are such extraribosomal functions of S4 known in plants and animals even as genetic evidence suggests that deficiency of S4X isoform in 46,XX human females may produce Turner syndrome (45,XO).
  
  
  METHODS
  Recombinant human S4X and rice S4 were used to determine their enzymatic action in the cleavage of synthetic peptide substrates and natural proteins. We also studied autoproteolysis of the recombinant S4 proteins, and examined the growth and proliferation of S4-transfected human embryonic kidney cells.
  
  
  RESULTS
  Extraribosomal enzyme nature of eukaryotic S4 is described. Both human S4X and rice S4 are cysteine proteases capable of hydrolyzing a wide spectrum of peptides and natural proteins of diverse origin. Whereas rice S4 also cleaves the -XXXD↓- consensus sequence assumed to be specific for caspase-9 and granzyme B, human S4 does not. Curiously, both human and rice S4 show multiple-site autoproteolysis leading to self-annihilation. Overexpression of human S4 blocks the growth and proliferation of transfected embryonic kidney cells, presumably due to the extraribosomal enzyme trait reported.
  
  
  CONCLUSIONS
  The S4 proteins of humans and rice, prototypes of eukaryota, are non-specific cysteine proteases in the extraribosomal milieu.
  
  
  CONCLUSIONS
  The enzyme nature of S4 is relevant toward understanding not only the origin of ribosomal proteins, but also processes in cell biology and diseases.
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
authors.forename: Babu
authors.initials: B
authors.lastname: Sudhamalla
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kumar
authors.forename: R Sunil
authors.initials: RS
authors.lastname: Kumar
authors.forename: Pulikallu
authors.initials: P
authors.lastname: Sashi
authors.forename: U Mahammad
authors.initials: UM
authors.lastname: Yasin
authors.forename: Dasari
authors.initials: D
authors.lastname: Ramakrishna
authors.forename: P Nageswara
authors.initials: PN
authors.lastname: Rao
authors.forename: Abani K
authors.initials: AK
authors.lastname: Bhuyan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D057056:Cysteine Proteases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D012275:Oryza / Q000235:genetics* / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D010940:Plant Proteins; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C031798:ribosomal protein S4; D057056:Cysteine Proteases; D053804:Granzymes; D053453:Caspase 9
keywords: Ac-LEHD↓-AFC; Cell growth and proliferation; Cysteine protease; E. coli ribosomal protein S4; EcS4; Human S4X isoform; IAA; Mb; N-CBZ-Phe-Arg-aminomethylcoumarin; N-acetyl-LEHD-7-amino-4-trifluoromethylcoumarin; Ribosomal protein S4; Z-FR↓-AMC; horse myoglobin; iodoacetic acid; rRNA; ribosomal RNA