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Positional proteomics reveals differences in N-terminal proteoform stability

Daria Fijalkowska (UGent) , Elvis Ndah (UGent) , Kris Gevaert (UGent) and Petra Van Damme (UGent)
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Abstract
To understand the impact of alternative translation initiation on a proteome, we performed a proteome-wide study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. By combining pulsed SILAC with N-terminal COFRADIC, we monitored the stability of 1,941 human N-terminal proteoforms, including 147N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. N-terminally truncated proteoforms were less abundant than canonical proteoforms and often displayed altered stabilities, likely attributed to individual protein characteristics, including intrinsic disorder, but independent of N-terminal amino acid identity or truncation length. We discovered that the removal of initiator methionine by methionine aminopeptidases reduced the stability of processed proteoforms, while susceptibility for N-terminal acetylation did not seem to influence protein turnover rates. Taken together, our findings reveal differences in protein stability between N-terminal proteoforms and point to a role for alternative translation initiation and co-translational initiator methionine removal, next to alternative splicing, in the overall regulation of proteome homeostasis.
Keywords
DEGRADATION, ACETYLTRANSFERASES, GENE-EXPRESSION, ACETYLATION, ENERGY CONTENT, CELLULAR-PROTEINS, COMPREHENSIVE RESOURCE, END RULE PATHWAY, MAMMALIAN-CELLS, ALTERNATIVE TRANSLATION INITIATION, protein stability, ribosome profiling, N-terminal proteoform, initiator methionine processing, alternative translation initiation

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Chicago
Fijałkowska, Daria, Elvis Ndah, Kris Gevaert, and Petra Van Damme. 2016. “Positional Proteomics Reveals Differences in N-terminal Proteoform Stability.” Molecular Systems Biology 12 (2).
APA
Fijałkowska, D., Ndah, E., Gevaert, K., & Van Damme, P. (2016). Positional proteomics reveals differences in N-terminal proteoform stability. MOLECULAR SYSTEMS BIOLOGY, 12(2).
Vancouver
1.
Fijałkowska D, Ndah E, Gevaert K, Van Damme P. Positional proteomics reveals differences in N-terminal proteoform stability. MOLECULAR SYSTEMS BIOLOGY. 2016;12(2).
MLA
Fijałkowska, Daria, Elvis Ndah, Kris Gevaert, et al. “Positional Proteomics Reveals Differences in N-terminal Proteoform Stability.” MOLECULAR SYSTEMS BIOLOGY 12.2 (2016): n. pag. Print.
@article{7222667,
  abstract     = {To understand the impact of alternative translation initiation on a proteome, we performed a proteome-wide study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. By combining pulsed SILAC with N-terminal COFRADIC, we monitored the stability of 1,941 human N-terminal proteoforms, including 147N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. N-terminally truncated proteoforms were less abundant than canonical proteoforms and often displayed altered stabilities, likely attributed to individual protein characteristics, including intrinsic disorder, but independent of N-terminal amino acid identity or truncation length. We discovered that the removal of initiator methionine by methionine aminopeptidases reduced the stability of processed proteoforms, while susceptibility for N-terminal acetylation did not seem to influence protein turnover rates. Taken together, our findings reveal differences in protein stability between N-terminal proteoforms and point to a role for alternative translation initiation and co-translational initiator methionine removal, next to alternative splicing, in the overall regulation of proteome homeostasis.},
  articleno    = {858},
  author       = {Fijalkowska, Daria and Ndah, Elvis and Gevaert, Kris and Van Damme, Petra},
  issn         = {1744-4292},
  journal      = {MOLECULAR SYSTEMS BIOLOGY},
  language     = {eng},
  number       = {2},
  pages        = {21},
  title        = {Positional proteomics reveals differences in N-terminal proteoform stability},
  url          = {http://dx.doi.org/10.15252/msb.20156662},
  volume       = {12},
  year         = {2016},
}

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