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Review
. 2023 Jan 19:13:1085408.
doi: 10.3389/fendo.2022.1085408. eCollection 2022.

Emerging role of UFMylation in secretory cells involved in the endocrine system by maintaining ER proteostasis

Yun Cheng  1 , Zikang Niu  2 , Yafei Cai  2 , Wei Zhang  2
Affiliations
Review

Emerging role of UFMylation in secretory cells involved in the endocrine system by maintaining ER proteostasis

Yun Cheng et al. Front Endocrinol (Lausanne). .

Abstract

Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like molecule (UBL) discovered almost two decades ago, but our knowledge about the cellular and molecular mechanisms of this novel protein post-translational modification is still very fragmentary. In this review, we first summarize the core enzymes and factors involved in the UFMylation cascade, which, similar to ubiquitin, is consecutively catalyzed by UFM1-activating enzyme 5 (UBA5), UFM1-conjugating enzyme 1 (UFC1) and UFM1-specific ligase 1 (UFL1). Inspired by the substantial implications of UFM1 machinery in the secretory pathway, we next concentrate on the puzzling role of UFMylation in maintaining ER protein homeostasis, intending to illustrate the underlying mechanisms and future perspectives. At last, given a robust ER network is a hallmark of healthy endocrine secretory cells, we emphasize the function of UFM1 modification in physiology and pathology in the context of endocrine glands pancreas and female ovaries, aiming to provide precise insight into other internal glands of the endocrine system.

Keywords: ER proteostasis; UFMylation; endocrine; ovaries; pancreas; secretory pathway.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ER proteostasis mechanisms of UFMylation. Functional relationships between components are indicated. The figure presents key components of the UFMylation pathway in the center of the regulatory network. Arrows indicate activation whereas bar-ended lines indicate inhibitory interactions. Broken lines indicate indirect interactions or interactions requiring further study.
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Grants and funding

Work in the authors’ laboratories has been supported by the Senior Health Research Project of Jiangsu Provincial Health Commission (LKM2023010 to YC), National Natural Science Foundation of China (No. 32270516, 31970413 and 31701229) and National Key R&D Program of China (2018YFC1200201).

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