Dataset Information

Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes

ABSTRACT: Protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2, and ubiquitin ligase E3. Uba1 was thought to be the only E1 until the recent identification of Uba6 as an alternative. To differentiate the biological functions of Uba1 and Uba6, we applied a novel orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells. By expressing pairs of an engineered ubiquitin and engineered Uba1 or Uba6 that were generated for exclusive interactions, we identified 697 Uba6 targets and 529 Uba1 targets with 258 overlaps. Bioinformatics revealed substantial differences in pathways involving Uba1- and Uba6-specific targets. We demonstrated that polyubiquitination and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1, and Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. These data reveal the distinctive substrate pools for Uba1 and Uba6 and manifest non-redundant biological roles for Uba6.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Early Embryonic Cell

SUBMITTER: Duc Duong

LAB HEAD: Hiroaki Kiyokawa

PROVIDER: PXD005513 | Pride | 2017-07-31

REPOSITORIES: Pride

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Publications

Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes.

Liu Xianpeng X Zhao Bo B Sun Limin L Bhuripanyo Karan K Wang Yiyang Y Bi Yingtao Y Davuluri Ramana V RV Duong Duc M DM Nanavati Dhaval D Yin Jun J Kiyokawa Hiroaki H

Nature communications 20170130

Protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Uba1 was thought to be the only E1 until the recent identification of Uba6. To differentiate the biological functions of Uba1 and Uba6, we applied an orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells. By expressing pairs of an engineered ubiquitin and engineered Uba1 or Uba6 that were generated for excl ...[more]

PMID: 28134249

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			Action	DRS
	hiro_pregg_fa6.msf	Msf
	hiro_pregg_fa6.raw	Raw
	hiro_pregg_fa6b.msf	Msf
	hiro_pregg_fa6b.raw	Raw
	hiro_pregg_fe1.msf	Msf