Functional analysis of ZFP36 proteins in keratinocytes

Prenzler, Frauke; Fragasso, Annunziata; Schmitt, Angelika; Munz, Barbara

doi:10.1016/j.ejcb.2016.04.007

Cited by 22 publications

(16 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ZFP36-knockout mice, macrophages lacking ZFP36 display increased tumor necrosis factor (TNF)-α mRNA stability and TNF-α production 10 . Other studies found that ZFP36 family proteins negatively regulate the mRNA stability of granulocyte macrophage colony-stimulating factor (GM-CSF) 11 , vascular endothelial growth factor (VEGF) 12 , 13 , cyclooxygenase (COX)-2 14 , cyclin D 15 , c-Myc 15 , and bcl-2 16 , 17 ;. Therefore, the functions of the ZFP36 family are linked to the regulation of inflammation, apoptosis, proliferation, and angiogenesis 18 .…”

Section: Introductionmentioning

confidence: 99%

ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner

Suk

Chang

Lin

et al. 2018

Sci Rep

View full text Add to dashboard Cite

ZFP36 family members include ZFP36, ZFP36L1, and ZFP36L2, which belong to CCCH-type zinc finger proteins with two tandem zinc finger (TZF) regions. Whether ZFP36L1 and ZFP36L2 have antiproliferative activities similar to that of ZFP36 is unclear. In this study, when ZFP36L1 or ZFP36L2 was overexpressed in T-REx-293 cells, cell proliferation was dramatically inhibited and the cell cycle was arrested at the G1 phase. The levels of cell-cycle-related proteins, including cyclin B, cyclin D, cyclin A, and p21, decreased; however, p53 increased in ZFP36L1-or ZFP36L2-overexpressing T-REx-293 cells. Forced expression of ZFP36L1 or ZFP36L2 also inhibited cell proliferation and cyclin D gene expression in three human colorectal cancer cell lines: HCT116 p53+/+, HCT116 p53−/−, and SW620 (mutated p53) cells. However, it increased p53 and p21 expression only in HCT116 p53+/+ cells. Knockdown of ZFP36L1 or ZFP36L2 increased cell proliferation and cyclin D expression; furthermore, the mutation of the TZF of ZFP36L1 or ZFP36L2 caused them to lose their antiproliferative ability, to the extent that they could not inhibit cyclin D expression in these three cell lines. The results indicated that ZFP36L1 and ZFP36L2 play a negative role in cell proliferation; the underlying mechanisms might be mediated through a cyclin D-dependent and p53-independent pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner

Suk

Chang

Lin

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It was recently reported that keratinocytes express TTP protein (14). We therefore generated mice with conditional deletion of TTP in keratinocytes (Zfp36 fl/fl K14-Cre mice, referred to herein as Zfp36 ΔEP mice).…”

Section: Resultsmentioning

confidence: 99%

Tristetraprolin expression by keratinocytes controls local and systemic inflammation

Andrianne

Assabban

et al. 2017

JCI Insight

View full text Add to dashboard Cite

Tristetraprolin (TTP, encoded by the Zfp36 gene) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL‑23 by myeloid cells, such as macrophages or DCs. Here, we generated mice with conditional deletion of TTP in keratinocytes (Zfp36fl/flK14-Cre mice, referred to herein as Zfp36ΔEP mice). Unlike DC-restricted (CD11c-Cre) or myeloid cell-restricted (LysM-Cre) TTP ablation, these mice developed exacerbated inflammation in the imiquimod-induced psoriasis model. Furthermore, Zfp36ΔEP mice progressively developed a spontaneous pathology with systemic inflammation, psoriatic-like skin lesions, and dactylitis. Finally, we provide evidence that keratinocyte-derived TNF production drives these different pathological features. In summary, these findings expand current views on the initiation of psoriasis and related arthritis by revealing the keratinocyte-intrinsic role of TTP.

show abstract

“…While the role of ZNF512 in tumor differentiation is not known, other members of the zinc finger family proteins are important players in cell differentiation. For example, ZFP637 inhibits differentiation of myoblast cells (Li et al, 2010) while ZFP36 knockdown is associated with increased expression of keratin 10, a known differentiation marker, in keratinocytes (Prenzler et al, 2016). These findings suggest potential value of these proteins as WD cSCC biomarkers and their roles in cSCC differentiation and malignancy.…”

Section: Protein Changes Corresponding To the Level Of Cscc Tumor Difmentioning

confidence: 99%

Data Independent Acquisition Proteomic Analysis Can Discriminate between Actinic Keratosis, Bowen’s Disease, and Cutaneous Squamous Cell Carcinoma

Azimi

Yang

Ali

et al. 2020

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Actinic keratosis, Bowen's disease and cutaneous squamous cell carcinoma (cSCC) are heterogeneous keratinocytic skin lesions. Biomarkers that can accurately stratify these lesion types are needed to support a new paradigm of personalized and precise management of skin neoplasia. In this paper, we used a data independent acquisition proteomics workflow, sequential window acquisition of all theoretical mass spectra, to analyze formalin-fixed paraffin-embedded samples of normal skin and keratinocytic skin lesions, including welldifferentiated, moderately differentiated and poorly differentiated cSCC lesions. We quantified 3,574 proteins across the 93 samples studied. Differential abundance analysis identified 19, 5, and 6 protein markers exclusive to actinic keratosis, Bowen's disease and cSCC lesions, respectively. Among cSCC lesions of various levels of tumor differentiation, 118, 230, and 17 proteins showed a potential as biomarkers of welldifferentiated, moderately differentiated and poorly differentiated cSCC lesions, respectively. Bioinformatics analysis revealed that actinic keratosis and cSCC lesions were associated with decreased apoptosis, and Bowen's disease lesions with over-representation of the DNA damage repair pathway. Differential expression of alternatively spliced FGFR2, Rho guanosine triphosphatase signaling, and RNA metabolism proteins were associated with the level of cSCC tumor differentiation. Proteome profiles also separated keratinocytic skin lesion subtypes on principal components analysis. Overall, protein markers have excellent potential to discriminate keratinocytic skin lesion subtypes and facilitate new diagnostic and therapeutic strategies.

show abstract

Functional analysis of ZFP36 proteins in keratinocytes

Cited by 22 publications

References 38 publications

ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner

ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner

Tristetraprolin expression by keratinocytes controls local and systemic inflammation

Data Independent Acquisition Proteomic Analysis Can Discriminate between Actinic Keratosis, Bowen’s Disease, and Cutaneous Squamous Cell Carcinoma

Contact Info

Product

Resources

About