Komori, R. | bioRxiv Science

bioRxiv2023

Expression of transcription factors KLF2 and KLF4 is induced by the mammalian Golgi stress response

The Golgi stress response is a homeostatic mechanism that augments Golgi function when Golgi function becomes insufficient (Golgi stress). Glycosylation of the core proteins of proteoglycans is one of the important functions of the Golgi. If the production of core proteins is increased and the amount of glycosylation enzymes for proteoglycans becomes insufficient (PG-type Golgi stress), the proteoglycan pathway of the Golgi stress response is activated, resulting in the transcriptional induction of glycosylation enzymes, including NDST2, HS6ST1 and GLCE. The transcriptional induction of these glycosylation enzymes is regulated by the enhancer element, PGSE-A; however, transcription factors that induce transcription from PGSE-A have not yet been identified. We herein proposed KLF2 and KLF4 as candidate transcription factors for transcriptional induction from PGSE-A, and revealed that their expression was up-regulated in response to PG-type Golgi stress. These results suggest that KLF2 and KLF4 are important regulators of the proteoglycan pathways of the mammalian Golgi stress response.

cell biology↗

bioRxiv2019

MGSE regulates crosstalk from the mucin pathway to the TFE3 pathway of the Golgi stress response

The Golgi apparatus is an organelle where membrane or secretory proteins receive post-translational modifications such as glycosylation and sulfation, after which the proteins are selectively transported to their final destinations through vesicular transport. When the synthesis of secretory or membrane proteins is increased and overwhelms the capacity of the Golgi (Golgi stress), eukaryotic cells activate a homeostatic mechanism called the Golgi stress response to augment the capacity of the Golgi. Four response pathways of the Golgi stress response have been identified, namely the TFE3, CREB3, HSP47, and proteoglycan pathways, which regulate the general function of the Golgi, apoptosis, cell survival, and proteoglycan glycosylation, respectively. Here, we identified a novel response pathway that augments the expression of glycosylation enzymes for mucins in response to insufficiency in mucin-type glycosylation in the Golgi (mucin-type Golgi stress), and we found that expression of glycosylation enzymes for mucins such as GALNT5, GALNT8, and GALNT18 was increased upon mucin-type-Golgi stress. We named this pathway the mucin pathway. Unexpectedly, mucin-type Golgi stress induced the expression and activation of TFE3, a key transcription factor regulating the TFE3 pathway, suggesting that the activated mucin pathway sends a crosstalk signal to the TFE3 pathway. We identified an enhancer element regulating transcriptional induction of TFE3 upon mucin-type Golgi stress, and named it the mucin-type Golgi stress response element, of which consensus was ACTTCC(N9)TCCCCA. These results suggested that crosstalk from the mucin pathway to the TFE3 pathway has an important role in the regulation of the mammalian Golgi stress response.

cell biology↗