The stability and oncogenic function of LIN28A are regulated by USP28

Haq, Saba; Das, Soumyadip; Kim, Dong Ho; Chandrasekaran, Arun Pandian; Hong, Seok Ho; Kim, Kye Seong; Ramakrishna, Suresh

doi:10.1016/j.bbadis.2018.12.006

Cited by 26 publications

(19 citation statements)

References 43 publications

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“…To evaluate the reproducibility and sensitivity of our LIN28A interactome, we surveyed the currently known LIN28A interactors from 23 papers ( Amen et al., 2017 ; Balzer and Moss, 2007 ; Butland et al., 2014 ; Chang et al., 2013 ; Choudhury et al., 2014 ; Cox et al., 2010 ; Haenig et al., 2020 ; Hagan et al., 2009 ; Haq et al., 2019 ; Hein et al., 2015 ; Heo et al., 2009 ; Huttlin et al., 2021 ; Jin et al., 2011 ; Kawahara et al., 2011 ; Li et al., 2014 ; Luck et al., 2020 ; Maier et al., 2015 ; Mallanna et al., 2010 ; Marcon et al., 2014 ; Närvä et al., 2012 ; Parisi et al., 2021 ; Polesskaya et al., 2007 ; Wang et al., 2019 ), covering more than the BioGRID ( Chatr-Aryamontri et al., 2017 ) and IntAct ( Orchard et al., 2014 ) databases ( Table S1 ). Among 581 previously reported LIN28A interactors, 207 proteins were re-identified in our NPC data.…”

Section: Resultsmentioning

confidence: 99%

Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

McClatchy

Diedrich

et al. 2021

iScience

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Summary A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPCs). We profiled the endogenous LIN28A-interacting proteins in NPCs differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Prompted by the interactome data, we revealed that LIN28A may impact the subcellular distribution of its interactors and stress granule formation upon oxidative stress. Overall, our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.

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Section: Resultsmentioning

confidence: 99%

Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

McClatchy

Diedrich

et al. 2021

iScience

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“…Methylation of LIN28A stimulates multimerization of LIN28A with primary let-7 (pri-let-7), thereby sequestering pri-let-7 in the nucleoli and blocking processing of let-7 in a TUTase-independent manner (Kim et al, 2014). More recently, it has been reported that a deubiquitinating enzyme ubiquitin-specific protease 28 interacts with and stabilizes LIN28A protein to extend its half-life, thus enhancing the LIN28A-mediated inhibition of endogenous let-7 processing (Haq et al, 2019). Here, we found that LIN28A was post-translationally modified by SUMO1 at K15 in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Migration mediated by LIN28A was determined by wound-healing assay (Haq et al, 2019). Serum-starved DU145 or T47D stable cell lines were cultured on 12well plates overnight for adhering.…”

Section: Migration Assay By Wound Healingyimentioning

confidence: 99%

SUMOylation modulates the LIN28A‐let‐7 signaling pathway in response to cellular stresses in cancer cells

et al. 2020

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LIN28A is a conserved RNA‐binding protein that inhibits the biogenesis of let‐7 microRNAs, thus promoting cancer progression. However, mechanisms underlying the activation of the LIN28A‐let‐7 signaling pathway remain poorly understood. Here, we show that LIN28A is SUMOylated in vivo and in vitro at K15, which is increased by hypoxia but reduced by chemotherapy drugs such as Cisplatin and Paclitaxel. SUMOylation of LIN28A aggravates its inhibition of let‐7 maturation, resulting in a stark reduction in let‐7, which promotes cancer cell proliferation, migration, invasion, and tumor growth in vivo. Mechanistically, SUMOylation of LIN28A increases its binding affinity with the precursor let‐7 (pre‐let‐7), which subsequently enhances LIN28A‐mediated recruitment of terminal uridylyltransferase TUT4 and simultaneously blocks DICER processing of pre‐let‐7, thereby reducing mature let‐7 production. These effects are abolished in SUMOylation‐deficient mutant LIN28A‐K15R. In summary, these findings shed light on a novel mechanism by which SUMOylation could regulate the LIN28A‐let‐7 pathway in response to cellular stress in cancer cells.

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“…USP28 increases aerobic glycolysis and promotes cell proliferation upon stabilization of FOXC1 [50]. Moreover, USP28 also stabilizes other oncoproteins (Table 2), such as STAT3 [48] or LIN28 [49], promoting cancer cell viability and growth.…”

Section: Usp28: Oncogene or Tumor Suppressor? The Importance Of Geneticsmentioning

confidence: 99%

USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma

Prieto-Garcia

Tomašković

Shah

et al. 2021

Cells

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Squamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damage repair, apoptosis and oncogenesis. In squamous cell carcinoma, USP28 is strongly expressed and stabilizes the essential squamous transcription factor ΔNp63, together with important oncogenic factors, such as NOTCH1, c-MYC and c-JUN. It is presumed that USP28 is an oncoprotein; however, recent data suggest that the deubiquitinase also has an antineoplastic effect regulating important tumor suppressor proteins, such as p53 and CHK2. In this review, we discuss: 1) The emerging role of USP28 in cancer. 2) The complexity and mutational landscape of squamous tumors. 3) The genetic alterations and cellular pathways that determine the function of USP28 in squamous cancer. 4) The development and current state of novel USP28 inhibitors.

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The stability and oncogenic function of LIN28A are regulated by USP28

Cited by 26 publications

References 43 publications

Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

SUMOylation modulates the LIN28A‐let‐7 signaling pathway in response to cellular stresses in cancer cells

USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma

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