The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition

Birte Kalveram, Gunter Schmidtke, Marcus Groettrup

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

During misfolded-protein stress, the cytoplasmic protein histone deacetylase 6 (HDAC6) functions as a linker between the dynein motor and polyubiquitin to mediate the transport of polyubiquitylated cargo to the aggresome. Here, we identify a new binding partner of HDAC6, the ubiquitin-like modifier FAT10 (also known as UBD), which is cytokine-inducible and - similar to ubiquitin - serves as a signal for proteasomal degradation. In vivo, the two proteins only interacted under conditions of proteasome impairment. The binding of HDAC6 to FAT10 was mediated by two separate domains: the C-terminal ubiquitin-binding zinc-finger (BUZ domain) of HDAC6 and its first catalytic domain, even though catalytic activity of HDAC6 was not required for this interaction. Both endogenous and ectopically expressed FAT10 as well as the model conjugate FAT10-GFP localized to the aggresome in a microtubule-dependent manner. Furthermore, FAT10-containing as well as ubiquitin-containing aggresomes were reduced in both size and number in HDAC6-deficient fibroblasts. We conclude that, if FAT10 fails to subject its target proteins to proteasomal degradation, an alternative route is taken to ensure their sequestration and possibly also their subsequent removal by transporting them to the aggresome via the association with HDAC6.

Original languageEnglish (US)
Pages (from-to)4079-4088
Number of pages10
JournalJournal of Cell Science
Volume121
Issue number24
DOIs
StatePublished - Dec 15 2008
Externally publishedYes

Fingerprint

Histone Deacetylases
Proteasome Endopeptidase Complex
Ubiquitin
Ubiquitin C
Polyubiquitin
Dyneins
Proteins
Zinc Fingers
Heat-Shock Proteins
Microtubules
Catalytic Domain
Fibroblasts
Cytokines

Keywords

  • Aggresome
  • FAT10
  • Histone deacetylase 6
  • Proteasome
  • Ubiquitin-like protein

ASJC Scopus subject areas

  • Cell Biology

Cite this

The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition. / Kalveram, Birte; Schmidtke, Gunter; Groettrup, Marcus.

In: Journal of Cell Science, Vol. 121, No. 24, 15.12.2008, p. 4079-4088.

Research output: Contribution to journalArticle

Kalveram, Birte ; Schmidtke, Gunter ; Groettrup, Marcus. / The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition. In: Journal of Cell Science. 2008 ; Vol. 121, No. 24. pp. 4079-4088.
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