Usage Information
Abstract
The RhoBTB1/Cullin-3 (CUL3) pathway in smooth muscle cells (SMCs) controls the ubiquitination and proteasomal degradation of target proteins that regulate vasodilation, vasoconstriction, and the actin cytoskeleton and, through this, blood pressure (BP) and arterial stiffness. Using proximity labeling coupled with mass spectrometry in A7R5 SMCs, we identified proteins that bound to the C-terminal half of RhoBTB1, which functions as an adaptor to deliver substrates to CUL3. We examined the physiological relevance of one of these substrates, RbFox2. Coimmunoprecipitation validated the interaction of RbFox2 with RhoBTB1. RbFox2 expression was elevated in response to inhibition of the ubiquitination-proteasomal pathway, CUL3 deficiency, and RhoBTB1 inhibition by either siRNA or angiotensin II (ANG). RbFox2 was ubiquitinated in a RhoBTB1- and CUL3-dependent manner, suggesting its regulation through the RhoBTB1/CUL3-dependent ubiquitin-proteasome pathway. Inhibition of RbFox2 impaired the actin cytoskeleton in A7R5 cells and in primary SMCs from RbFox2fl/fl mice and decreased the levels of globular and filamentous actin. ANG increased BP and arterial stiffness of RbFox2fl/fl mice, but the progression of arterial stiffness was halted after SMC-specific RbFox2 deletion despite a continued rise in BP. We conclude that RhoBTB1 and RbFox2 are important regulators of arterial stiffness through a mechanism that influences cytoskeletal integrity.
Authors
Gaurav Kumar, Nisita Chaihongsa, Daniel T. Brozoski, Daria Golosova, Ibrahim Vazirabad, Ko-Ting Lu, Kelsey K. Wackman, Ravi K. Singh, Curt D. Sigmund
Usage data is cumulative from April 2026 through June 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,114 | 0 |
| 379 | 0 | |
| Figure | 285 | 0 |
| Supplemental data | 442 | 0 |
| Citation downloads | 230 | 0 |
| Totals | 2,450 | 0 |
| Total Views | 2,450 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
