SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway

Li, Shujing; Wang, Jin; Hu, Gaolei; Aman, Sattout; Li, Bowen; Li, Yanan; Xia, Kangkai; Yang, Yanchun; Ahmad, Bashir; Wang, Miao; Wu, Harry X.

doi:10.1016/j.cellsig.2020.109686

Cited by 15 publications

(11 citation statements)

References 46 publications

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“…Recent studies have revealed that MCL1 degradation is regulated partly through phosphorylation of the PEST domain by GSK3β, JNK, p38, CK2, CDK1, and CDK5 [71][72][73][74][75] through proteasomal degradation. The ubiquitination of MCL1 is controlled by multiple E3 ligases, including MULE [76], SCF β-TRCP [77], APC/C Cdc20 [74], SCF FBW7 [72,73], TRIM17 [78], TRIM11 [79], FBXO4 [80], and Parkin [81,82]. Notably, SCF β-TRCP , SCF FBW7 , and APC/C Cdc20 require prior phosphorylation for MCL1 ubiquitination and degradation.…”

Section: Regulation Of the Mcl1 Pathwaymentioning

confidence: 99%

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Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease

Rezaeian

Wei

Inuzuka

2022

Acta Materia Medica

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Maintaining neuronal integrity and function requires precise mechanisms controlling organelle and protein quality. Alzheimer’s disease (AD) is also characterized by functional defects in the clearance and recycling of intracellular components. In fact, neuronal homeostasis involves autophagy, mitophagy, apoptosis, and compromised activity in these cellular processes may cause pathological phenotypes of AD. Therefore, mitophagy is a critical mitochondrial quality-control system, and impaired mitophagy is a hallmark of AD. Myeloid cell leukemia 1 (MCL1), a member of the pro-survival B-cell lymphoma protein 2 (BCL2) family, is a mitochondrially targeted protein that contributes to maintaining mitochondrial integrity. Mcl1-knockout mice display peri-implantation lethality. Studies on conditional Mcl1-knockout mice have demonstrated that MCL1 plays a central role in neurogenesis and neuronal survival during brain development. Accumulating evidence indicates the critical role of MCL1 as a regulator of neuronal autophagy, mitophagy, and survival. In this review, we discuss the emerging neuroprotective function of MCL1 and how dysregulation of MCL1 signaling is involved in the pathogenesis of AD. Because members of the pro-survival BCL2 family proteins are promising targets of pharmacological intervention with BH3 mimetic drugs, we also discuss the promise of MCL1-targeting therapy in AD.

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Section: Regulation Of the Mcl1 Pathwaymentioning

confidence: 99%

“…Similarly to ubiquitination, SUMOylation regulates various cellular processes. MCL1 is a target of SUMOylation, which counteracts MCL1 ubiquitination, thus leading to MCL1 stabilization [79]. Furthermore, MCL1 has been reported to undergo acetylation [89].…”

Section: Regulation Of the Mcl1 Pathwaymentioning

confidence: 99%

Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease

Rezaeian

Wei

Inuzuka

2022

Acta Materia Medica

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“…Myeloid cell leukemia 1 (MCL1), an anti-apoptotic protein that belongs to the Bcl-2 family, maintains its stability via its SUMOylation at sites K234 and K238, and inhibits TRIM11-mediated ubiquitination of MCL1 and cancer cell apoptosis ( 149 ). Moreover, death domain associated protein (DAXX) has been shown to contain SIMs, and phosphorylation of DAXX-SIM promotes SUMOylation by binding to SUMO1 and SUMO2/3, thereby enhancing stress-induced apoptosis via inhibiting anti-apoptotic genes ( 150 , 151 ).…”

Section: Adaptive Mechanisms Of Sumo-mediated Tumorigenesis and Drug Resistance In MMmentioning

confidence: 99%

Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review)

Qian

Yang

2021

Int J Oncol

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The small ubiquitin-like modifier (SUMO) system serves an important role in the regulation of protein stability and function. SUMOylation sustains the homeostatic equilibrium of protein function in normal tissues and numerous types of tumor. Accumulating evidence has revealed that SUMO enzymes participate in carcinogenesis via a series of complex cellular or extracellular processes. The present review outlines the physiological characteristics of the SUMOylation pathway and provides examples of SUMOylation participation in different cancer types, including in hematological malignancies (leukemia, lymphoma and myeloma). It has been indicated that the SUMO pathway may influence chromosomal instability, cell cycle progression, apoptosis and chemical drug resistance. The present review also discussed the possible relationship between SUMOylation and carcinogenic mechanisms, and evaluated their potential as biomarkers and therapeutic targets in the diagnosis and treatment of hematological malignancies. Developing and investigating inhibitors of SUMO conjugation in the future may offer promising potential as novel therapeutic strategies.

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“…Myeloid cell leukemia 1(MCL1), an anti-apoptotic protein that belongs to the BCL-2 family, often keeps a high expression in many cancers during oncogenesis. The stability of MCL1 is maintained by SUMOylation at its K234 and K238 sites, which inhibits Tripartite motif-containing 11(TRIM11) -mediate ubiquitination of MCL1 and apoptosis of cancer cells (Li et al 2020).…”

Section: The Crosstalk Between Sumo Modification and Apoptosismentioning

confidence: 99%

SUMO modification in apoptosis

Jing

Wang

et al. 2020

J Mol Histol

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Apoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular organism. Fail to remove apoptotic cells often lead to homeostasis imbalance, fatal autoimmune diseases, and neurodegenerative diseases. Small ubiquitin-related modifiers (SUMOs) modification is a post-translational modification of ubiquitin proteins mediated by the sentrin-specific proteases (SENPs) family. SUMO modification is widely involved in many cellular biological process, and abnormal SUMO modification is also closely related to many major human diseases. Recent researches have revealed that SUMO modification event occurs during apoptosis and clearance of apoptotic cells, and plays an important role in the regulation of apoptotic signaling pathways. This review summarizes some recent progress in the revelation of regulatory mechanisms of these pathways and provides some potential researching hotpots of the SUMO modification regulation to apoptosis.

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SUMOylation of MCL1 protein enhances its stability by regulating the ubiquitin-proteasome pathway

Cited by 15 publications

References 46 publications

Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease

Regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer’s disease

Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review)

SUMO modification in apoptosis

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