Sumoylation Is Important for Stability, Subcellular Localization, and Transcriptional Activity of SALL4, an Essential Stem Cell Transcription Factor

Yang, Fan; Yao, Yixin; Jiang, Yongping; Lu, Luo; Ma, Yupo; Dai, Wei

doi:10.1074/jbc.m112.391441

Cited by 28 publications

(24 citation statements)

References 42 publications

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“…Expression of SALL4B mutants with deletions of 3 lysine-rich regions (fragments of 258-317, 127-156, or 578-601) did not cause an apparent change in its subcellular localization compared with the wild-type counterpart. Moreover, mutations (4R) of those lysine residues required for SUMO-modification 11 did not affect the subcellular localization either. However, when lysine 64 was mutated into arginine (K64R), HA signals were detected primarily in the cytosol (Fig.…”

Section: Resultsmentioning

confidence: 91%

“…10,11 SALL4A is spliced from all 4 exons and encodes a protein containing 8 C2H2 zinc-finger domains. However, SALL4B lacks a large portion of exon 2 and encodes a protein containing 6 C2H2 zinc finger domains.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] SALL4B is a major splicing variant product of SALL4 and possesses full transcriptional activity. 10,11 Mutations of SALL4 gene are associated with several developmental syndromes, including Okihiro syndrome, acro-renalocular syndrome, and IVIC syndrome. 12 Aberrant expression of SALL4 is associated with development of various types of malignancies.…”

Section: Introducitonmentioning

confidence: 99%

“…4,5,19,21,22 SALL4 positively regulates OCT4 gene expression through binding to the conserved regulatory region of the OCT4 promoter. 5,11 On the other hand, SALL4…”

Section: Introducitonmentioning

confidence: 99%

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Identification of the nuclear localization signal of SALL4B, a stem cell transcription factor

Yang

Ren

et al. 2014

Cell Cycle

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Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introducitonmentioning

confidence: 99%

“…4,5,19,21,22 SALL4 positively regulates OCT4 gene expression through binding to the conserved regulatory region of the OCT4 promoter. 5,11 On the other hand, SALL4…”

Section: Introducitonmentioning

confidence: 99%

See 2 more Smart Citations

Identification of the nuclear localization signal of SALL4B, a stem cell transcription factor

Yang

Ren

et al. 2014

Cell Cycle

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“…Sumoylation plays a role in regulating the subcellular localization of target proteins [25][26][27][28][29] To determine whether sumoylation played a role in regulating subcellular localization of Mus81, HeLa cells were transfected with GFP-tagged WT Mus81 or its Mus81-5R for 48 h. Cells were then fixed and stained with antibody against GFP. Fluorescence microscopy showed that both GFP-Mus81 and GFP-Mus81-5R was primarily located to the nucleus, and when the expression level was high, GFP-Mus81 and GFP-Mus81-5R mutant were enriched in nucleoli during interphase (Fig 3S).…”

Section: Sumo-resistant Mutant Induces Misaligned Chromosomes In Mitomentioning

confidence: 99%

Arsenic-induced sumoylation of Mus81 is involved in regulating genomic stability

Yang

et al. 2017

Cell Cycle

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Chronic environmental exposure to metal toxicants such as chromium and arsenic is closely related to the development of several types of common cancers. Genetic and epigenetic studies in the past decade reveal that post-translational modifications of histones play a role in metal carcinogenesis. However, exact molecular mechanisms of metal carcinogenesis remain to be elucidated. In this study we found that As 2 O 3 , an environmental metal toxicant, upregulated overall modifications of many cellular proteins by SUMO2/3. Sumoylated proteins from arsenic-treated cells constitutively expressing His 6 -SUMO2 were pulled down by Ni-IDA resin under denaturing conditions. Mass spectrometric analysis revealed over 100 proteins that were potentially modified by sumoylation. Mus81, a DNA endonuclease involved in homologous recombination repair, was among the identified proteins whose sumoylation was increased after treatment with As 2 O 3. We further showed that K10 and K524 were 2 lysine residues essential for Mus81 sumoylation. Moreover, we demonstrated that Mus81 sumoylation is important for normal mitotic chromosome congression and that cells expressing SUMO-resistant Mus81 mutants displayed compromised DNA damage responses after exposure to metal toxins such as Cr(VI) and arsenic.

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The new advance of SALL4 in cancer: Function, regulation, and implication

Abouelnazar

Zhang

Wang

et al. 2023

Clinical Laboratory Analysis

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SALL4 (split-like protein 4) is a member of the mammalian homologs of the Drosophila homoeotic gene spalt (sal) and acts as a zinc finger transcription factor to govern the self-renewal and pluripotency of embryonic stem cells. SALL4 expression gradually decreases during development and is even absent in most adult tissues. However, increasing evidence suggests that SALL4 expression is restored in human cancers and its aberrant expression is associated with the progression of many hematopoietic malignancies and solid tumors. The potent roles of SALL4 in regulating cancer cell proliferation, apoptosis, metastasis, and drug resistance have been reported. SALL4 plays a dual role in epigenetic modulation by acting as either an activator or a repressor of its target genes. Furthermore, SALL4 interacts with other partners to control the expression of many downstream genes and the activation of various key signaling transduction pathways. SALL4 is considered as a promising diagnostic and prognostic biomarker and therapeutic target for cancer. In this review, we highlighted the major advances in the roles and mechanisms of SALL4 in cancer and the therapeutic strategies for targeting SALL4 to treat cancer.

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Sumoylation Is Important for Stability, Subcellular Localization, and Transcriptional Activity of SALL4, an Essential Stem Cell Transcription Factor

Cited by 28 publications

References 42 publications

Identification of the nuclear localization signal of SALL4B, a stem cell transcription factor

Identification of the nuclear localization signal of SALL4B, a stem cell transcription factor

Arsenic-induced sumoylation of Mus81 is involved in regulating genomic stability

The new advance of SALL4 in cancer: Function, regulation, and implication

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