E3 SUMO-protein ligase PIAS4

Definition:

Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity). Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR). Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin.

References:

[1]. Lalitha Subramanian, et al. A synergy control motif within the attenuator domain of CCAAT/enhancer-binding protein alpha inhibits transcriptional synergy through its PIASy-enhanced modification by SUMO-1 or SUMO-3. J Biol Chem. 2003 Mar 14;278(11):9134-41. [Content Brief]

[2]. Hideki Yamamoto, et al. Sumoylation is involved in beta-catenin-dependent activation of Tcf-4. EMBO J. 2003 May 1;22(9):2047-59. [Content Brief]

[3]. Y Shinbo, et al. Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. Cell Death Differ. 2006 Jan;13(1):96-108. [Content Brief]

[4]. B Liu, et al. A transcriptional corepressor of Stat1 with an essential LXXLL signature motif. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3203-7. [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]. Motomasa Ihara, et al. SUMO-1 modification of PIASy, an E3 ligase, is necessary for PIASy-dependent activation of Tcf-4. Mol Cell Biol. 2005 May;25(9):3506-18. [Content Brief]

[7]. Jannie Rendtlew Danielsen, et al. DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. J Cell Biol. 2012 Apr 16;197(2):179-87. [Content Brief]

[8]. V Nelson, et al. A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis. Apoptosis. 2001 Jun;6(3):221-34. [Content Brief]

[9]. Øyvind Dahle, et al. Transactivation properties of c-Myb are critically dependent on two SUMO-1 acceptor sites that are conjugated in a PIASy enhanced manner. Eur J Biochem. 2003 Mar;270(6):1338-48. [Content Brief]

[10]. Lin Cong, et al. SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function. J Biol Chem. 2011 Dec 23;286(51):43793-43808. [Content Brief]

[11]. Shan-Shan Gao, et al. TIP60 K430 SUMOylation attenuates its interaction with DNA-PKcs in S-phase cells: Facilitating homologous recombination and emerging target for cancer therapy. Sci Adv. 2020 Jul 10;6(28):eaba7822. [Content Brief]

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