E3 ubiquitin-protein ligase RNF4

Definition:

E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation. Catalyzes ubiquitination of sumoylated PARP1 in response to PARP1 trapping to chromatin, leading to PARP1 removal from chromatin by VCP/p97.

References:

[1]. Baoqiang Guo, et al. Extracellular signal-regulated kinase mitogen-activated protein kinase signaling initiates a dynamic interplay between sumoylation and ubiquitination to regulate the activity of the transcriptional activator PEA3. Mol Cell Biol. 2009 Jun;29(11):3204-18. [Content Brief]

[2]. Nadine Martin, et al. PARP-1 transcriptional activity is regulated by sumoylation upon heat shock. EMBO J. 2009 Nov 18;28(22):3534-48. [Content Brief]

[3]. Debaditya Mukhopadhyay, et al. The SUMO protease SENP6 is essential for inner kinetochore assembly. J Cell Biol. 2010 Mar 8;188(5):681-92. [Content Brief]

[4]. Marie-Claude Geoffroy, et al. Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies. Mol Biol Cell. 2010 Dec;21(23):4227-39. [Content Brief]

[5]. Dragomir B Krastev, et al. The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin. Nat Cell Biol. 2022 Jan;24(1):62-73. [Content Brief]

[6]. Michael H Tatham, et al. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. [Content Brief]

[7]. Martijn van Hagen, et al. RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha. Nucleic Acids Res. 2010 Apr;38(6):1922-31. [Content Brief]

[8]. Frank J Kaiser, et al. The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPS1 transcription factor. J Biol Chem. 2003 Oct 3;278(40):38780-5. [Content Brief]

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