A Comprehensive Review of Biological Roles and Interactions of Cullin-5 Protein

Abstract

Ubiquitination is a modification of proteins that has a powerful impact on protein function along with other cellular functions. This reaction is regulated through major enzymes, including E3 ligase as a chief enzyme. The Cullin-5 ubiquitin ligase (Cul5) possesses a variety of substrates that maintain the process of ubiquitination as well as proteasomal degradation. It regulates cell development, proliferation, and other physiological tasks in the human body. Moreover, it has been discovered that the expression of Cul5 plays a significant role in specific cancer cells while affecting the progression of tumor cells. This review is based on current knowledge about Cul5 and its expression, signaling pathways, regulation, virus-related responses, and inhibitors for therapeutic strategies.

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis

“…CUL5 is a Cullin-RING (CRL) E3 ubiquitin ligase that is best known for its role in regulating aspects of viral infection, especially for HI [39][40][41] . CUL5 serves as a scaffold for facilitating ubiquitin transfer from an E2 ligase to CUL5 substrates.…”

Cullin 5 aggravates hypoxic pulmonary hypertension by activating TRAF6/NF-κB/HIF-1α/VEGF

“…Cul 5 is currently regarded as a promising drug target molecule because of its various biological roles. 25 In this study we showed that Cul 5 promotes angiogenesis and cell adhesion. Cul 5 is the key component of Cullin-RING ligase-5 (CRL-5), and activation of CRL-5 requires Cul 5 neddylation, which is catalyzed by a neddylation enzyme cascade, consisting of the E1 NEDD8-activating enzyme, the E2 neddylation conjugating enzyme, and E3 neddylation ligase, 35 , 36 thus, neddylation inhibitor could inactive Cul 5.…”

“…TRAF6 is a substrate of Cul 5, 25 and it has also been reported that the Cul 5−TRAF6 interaction activates NF-κB signaling. 12 The TRAF6/NF-κB pathway is involved in many diseases, such as cancer, 31 lung injury, 32 and myocardial injury.…”

“…Seven different types of Cul proteins have been identified in human cells (Cul 1, Cul 2, Cul 3, Cul 4A, Cul 4B, Cul 5, Cul 7, and Cul 9), each of which engages a family of substrate receptors to assemble active CRLs, which are crucial in the cardiovascular system. 24 In addition, Cul 5 has been identified to play positive roles in regulating cell growth, proliferation and physiological and other processes in the human body 25 and is expressed in many cells and organs, including endothelial cells, brain, kidney collecting tubule cells, and vascular endothelial cells. 11 , 26 While the importance of CRL5-dependent protein ubiquitination in cancers has been well-documented, 27 what role each CRL5 plays in the cardiovascular system has just started to come to light, our study demonstrated for the first time that Cul 5 participates in the pathogenesis of HPH.…”

Protein Stability Regulation in Osteosarcoma: The Ubiquitin-like Modifications and Glycosylation as Mediators of Tumor Growth and as Targets for Therapy

“…mTOR signaling can be increased by K48-ubiqutination and degradation of DEP-domain containing mTOR-interacting protein (DEPTOR); a negative regulator of mTOR, able to act on both mTORC1 and mTORC2 [ 33 ]. DEPTOR is ubiquitinated either by the activity of the E3 ligases CUL5 [ 34 ] or Ring Finger Protein 7 (RNF7) [ 35 ]. This results in the increase of mTOR levels and in the inactivation of the autophagic process [ 36 , 37 ].…”