The USP21 short variant (USP21SV) lacking NES, located mostly in the nucleus in vivo, activates transcription by deubiquitylating ubH2A in vitro

Hiroshi Okuda; Hideki Ohdan; Manabu Nakayama; Haruhiko Koseki; Takeya Nakagawa; Takashi Ito

doi:10.1371/journal.pone.0079813

The USP21 short variant (USP21SV) lacking NES, located mostly in the nucleus in vivo, activates transcription by deubiquitylating ubH2A in vitro

PLoS One. 2013 Nov 22;8(11):e79813. doi: 10.1371/journal.pone.0079813. eCollection 2013.

Authors

Hiroshi Okuda¹, Hideki Ohdan, Manabu Nakayama, Haruhiko Koseki, Takeya Nakagawa, Takashi Ito

Affiliation

¹ Department of Biochemistry, Nagasaki University School of Medicine, Nagasaki, Japan ; Department of Surgery, Hiroshima University School of Medicine, Hiroshima, Japan.

Abstract

USP21 is a deubiquitylase that catalyzes isopeptide bond hydrolysis between ubiquitin and histone H2A. Since ubiqutylated H2A (ubH2A) represses transcription, USP21 plays a role in transcriptional activation. On the other hand, the localization of USP21 suggests it has an additional function in the cytoplasm. Here, we identified a USP21 short variant (USP21SV) lacking a nuclear export signal (NES). Differential localization of USP21SV, more in the nucleus than the USP21 long variant (USP21LV), suggests they have redundant roles in the cell. Ectopic expression of both USP21 variants decreased ubH2A in the nucleus. Furthermore, both recombinant USP21 variants activate transcription by deubiquitylating ubH2A in vitro. These data suggest multiple roles for USP21 in the ubiquitylation-deubiquitylation network in the cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cell Nucleus / metabolism*
Fluorescent Antibody Technique
Histones / metabolism*
Humans
Mice
Sequence Alignment
Ubiquitin Thiolesterase / genetics
Ubiquitin Thiolesterase / metabolism*

Substances

Histones
USP21 protein, human
Ubiquitin Thiolesterase

Grants and funding

This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas (grant number 24118003) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan and Grant-in-Aid for Scientific Research (B) (grant number 21390085) from Japan Society for the Promotion of Science (JSPS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.