Proteomics

Dataset Information

0

DUSP12 promotes cell cycle progression and protects cells from cells from ZNF622 mediated apoptosis


ABSTRACT: Protein phosphatases are critical for regulating cell signaling, cell cycle, and cell fate decisions, and their dysregulation leads to an array of human diseases like cancer. The dual specificity phosphatases (DUSPs) have emerged as important factors driving tumorigenesis and cancer therapy resistance. DUSP12 is a poorly characterized atypical DUSP widely conserved throughout evolution. Although no direct substrate has been firmly established, DUSP12 has been implicated in protecting cells from stress, regulating ribosomal biogenesis, and modulating cellular DNA content. In this study, we used affinity- and proximity-based biochemical purification approaches coupled to mass spectrometry to identify the zinc finger protein ZNF622 as a novel DUSP12 interactor, which was validated by in cell and in vitro IP assays. Interestingly, ZNF622 binds to the unique zinc-binding domain of DUSP12, which previous reports indicated was important for many of DUSP12’s functions within the cell. Prior studies had implicated ZNF622 as a modulator of apoptosis, but it remained unclear if and how ZNF622 participated in the cell cycle and, more so, how it promoted cell death. Using mass spectrometry analyses, we found that overexpression of DUSP12 promoted de-phosphorylation of ZNF622 at Ser 143 . Overexpression of ZNF622, but not Ser 143 phosphomimetic and phosphorylation-deficient mutants, led to an increase in pre-metaphase mitotic defects while knockdown of DUSP12 also showed mitotic defects in metaphase. Furthermore, knockdown of DUSP12 promoted, while knockdown of ZNF622 suppressed, stress-induced apoptosis. Our results support a model where DUSP12 protects cells from ZNF622 mediated stress-induced apoptosis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Cervix Squamous Epithelium

DISEASE(S): Cervix Carcinoma

SUBMITTER: Mehdi Bouhaddou  

LAB HEAD: Mehdi Bouhaddou

PROVIDER: PXD072946 | Pride | 2026-04-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20251222_162833_2025-12-22_JTO4_AB.sne Other
20251222_163042_2025-12-22_JTO4_PH.sne Other
FeatureLevelData_AB.csv Csv
FeatureLevelData_PH.csv Csv
ProteinLevelData_AB.csv Csv
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Publications


Protein phosphatases are critical for regulating cell signaling, cell cycle, and cell fate decisions, and their dysregulation leads to an array of human diseases like cancer. The dual specificity phosphatases (DUSPs) have emerged as important factors driving tumorigenesis and cancer therapy resistance. DUSP12 is a poorly characterized atypical DUSP widely conserved throughout evolution. Although no direct substrate has been firmly established, DUSP12 has been implicated in protecting cells from  ...[more]

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