TY - JOUR
T1 - KLHL7 promotes TUT1 ubiquitination associated with nucleolar integrity
T2 - Implications for retinitis pigmentosa
AU - Kim, Jaehyun
AU - Tsuruta, Fuminori
AU - Okajima, Tomomi
AU - Yano, Sarasa
AU - Sato, Ban
AU - Chiba, Tomoki
N1 - Funding Information:
We thank Dr. Mitsuru Okuwaki (University of Tsukuba, Japan) for anti-NPM1 antibody. We thank Mercel Diallo for critical reading of the manuscript, and Thomas Saddouk and members of laboratory for technical support and helpful discussions. This work was supported by Grant-in-Aid from Ministry of Education, Science, Sports and Culture of Japan (JSPS KAKENHI 23770218 to FT).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12/9
Y1 - 2017/12/9
N2 - Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. Recent studies have revealed that mutations in klhl7 gene cause several disorders, such as retinitis pigmentosa (RP). Although KLHL7 is considered to be crucial for regulating the protein homeostasis, little is known about its biological functions. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. TUT1 is normally localized in nucleolus; however, expression of KLHL7 facilitates a vulnerability of nucleolar integrity, followed by a decrease of TUT1 localization in nucleolus. On the other hand, pathogenic KLHL7 mutants, which causes an onset of RP, have little effect on both nucleolar integrity and TUT1 localization. Finally, KLHL7 increases TUT1 ubiquitination levels. Taken together, these results imply that KLHL7 is a novel regulator of nucleolus associated with TUT1 ubiquitination. Our study may provide a valuable information to elucidate a pathogenic mechanism of RP.
AB - Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. Recent studies have revealed that mutations in klhl7 gene cause several disorders, such as retinitis pigmentosa (RP). Although KLHL7 is considered to be crucial for regulating the protein homeostasis, little is known about its biological functions. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. TUT1 is normally localized in nucleolus; however, expression of KLHL7 facilitates a vulnerability of nucleolar integrity, followed by a decrease of TUT1 localization in nucleolus. On the other hand, pathogenic KLHL7 mutants, which causes an onset of RP, have little effect on both nucleolar integrity and TUT1 localization. Finally, KLHL7 increases TUT1 ubiquitination levels. Taken together, these results imply that KLHL7 is a novel regulator of nucleolus associated with TUT1 ubiquitination. Our study may provide a valuable information to elucidate a pathogenic mechanism of RP.
KW - KLHL7
KW - Nucleolus
KW - Retinitis pigmentosa
KW - TUT1
KW - Ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=85031718708&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.10.049
DO - 10.1016/j.bbrc.2017.10.049
M3 - Article
C2 - 29032201
AN - SCOPUS:85031718708
VL - 494
SP - 220
EP - 226
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1-2
ER -