|  Help  |  About  |  Contact Us

Publication : The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease.

First Author  Cortés-Montero E Year  2019
Journal  Antioxid Redox Signal Volume  31
Issue  7 Pages  503-520
PubMed ID  31088288 Mgi Jnum  J:298016
Mgi Id  MGI:6457166 Doi  10.1089/ars.2019.7724
Citation  Cortes-Montero E, et al. (2019) The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease. Antioxid Redox Signal 31(7):503-520
abstractText  Aims: Histidine triad nucleotide-binding protein 1 (HINT1) exhibits proapoptotic and tumor-suppressive activity. HINT1 binds to transcription factors such as teneurin1 and to the regulator of G protein signaling 17 (RGS) (Z2) protein, which incorporates the small ubiquitin-like modifier (SUMO), and is implicated in several types of cancer. HINT1 interacts with proteins such as PKCgamma and Raf-1 through zinc ions provided by the cysteine-rich domain of RGSZ2 and the coupled neural nitric oxide synthase (nNOS). Recently, a series of HINT1 mutants have been reported to cause human autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM). However, the specific alteration in the function of HINT1 induced by these mutants remains to be elucidated. Because sumoylation modifies protein association and transcriptional regulation, we investigated whether HINT1 exhibits zinc- and redox-regulated sumoylase activity, which may be altered in those mutants. Results: HINT1 exhibits cysteine protease activity to remove SUMO from a variety of signaling proteins. HINT1 sumoylase activity is blocked by zinc, and it is released by nitric oxide or calcium-activated calmodulin (CaM). HINT1 contains a SUMO-interacting motif (110-116 HIHLHVL) and the catalytic triad Cys84-Asp87-His114 in the C-terminal region. Thus, zinc probably provided by the RGSZ2-nNOS complex may bind to Cys84 to block HINT1 isopeptidase activity. Innovation: To date, HINT1 is the only sumoylase that is regulated by two alternate pathways, redox- and calcium-activated CaM. Conclusion: The 15 human HINT1 mutants reported to cause ARAN-NM exhibited altered sumoylase activity, which may contribute to the onset of this human motor disease.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

21 Bio Entities

Trail: Publication

0 Expression