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Pablo Di Giusto

Bio: Pablo Di Giusto is an academic researcher from National University of Cordoba. The author has contributed to research in topics: Secretory pathway & Golgi apparatus. The author has an hindex of 2, co-authored 3 publications receiving 45 citations. Previous affiliations of Pablo Di Giusto include National Scientific and Technical Research Council.

Papers
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Journal ArticleDOI
TL;DR: An overview of the diverse functions of each member of the CREB3 family of transcription factors with special focus on their role in the central nervous system is provided.
Abstract: CREB3 family of transcription factors are ER localized proteins that belong to the bZIP family. They are transported from the ER to the Golgi, cleaved by S1P and S2P proteases and the released N-terminal domains act as transcription factors. CREB3 family members regulate the expression of a large variety of genes and according to their tissue-specific expression profiles they play, among others, roles in acute phase response, lipid metabolism, development, survival, differentiation, organelle autoregulation, and protein secretion. They have been implicated in the ER and Golgi stress responses as regulators of the cell secretory capacity and cell specific cargos. In this review we provide an overview of the diverse functions of each member of the family (CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4) with special focus on their role in the central nervous system.

61 citations

Journal ArticleDOI
TL;DR: CREB3L1 has a role during the adaptation of the secretory pathway in response to high secretory demand in thyroid cells, a process with direct impact on thyroid physiology.
Abstract: Many secretory cells increase the synthesis and secretion of cargo proteins in response to specific stimuli. How cells couple increased cargo load with a coordinate rise in secretory capacity to ensure efficient transport is not well understood. We used thyroid cells stimulated with thyrotropin (TSH) to demonstrate a coordinate increase in the production of thyroid-specific cargo proteins and ER-Golgi transport factors, and a parallel expansion of the Golgi complex. TSH also increased expression of the CREB3L1 transcription factor, which alone caused amplified transport factor levels and Golgi enlargement. Furthermore, CREB3L1 potentiated the TSH-induced increase in Golgi volume. A dominant-negative CREB3L1 construct hampered the ability of TSH to induce Golgi expansion, implying that this transcription factor contributes to Golgi expansion. Our findings support a model in which CREB3L1 acts as a downstream effector of TSH to regulate the expression of cargo proteins, and simultaneously increases the synthesis of transport factors and the expansion of the Golgi to synchronize the rise in cargo load with the amplified capacity of the secretory pathway.

22 citations

Journal ArticleDOI
TL;DR: In this paper, the expression and signaling mechanism of CREB3 transcription factor family members were analyzed using the NGF-induced PC12 cell differentiation model, showing that NGF treatment causes Golgi enlargement and a parallel increased expression of proteins and mRNAs encoding for proteins required for membrane transport (transport factors).
Abstract: Nerve growth factor (NGF) stimulates numerous cellular physiological processes, including growth, differentiation, and survival, and maintains the phenotype of several neuronal types. Most of these NGF-induced processes require adaptation of the secretory pathway since they involve extensive remodeling of membranes and protein redistribution along newly formed neuritic processes. CREB3 transcription factors have emerged as signaling hubs for the regulation of numerous genes involved in the secretory pathway and Golgi homeostasis, integrating stimuli from multiple sources to control secretion, posttranslational modifications and trafficking of proteins. Although recent studies have focused on their role in the central nervous system, little is known about their participation in cell differentiation. Therefore, we aimed to analyze the expression and signaling mechanism of CREB3 transcription factor family members, using the NGF-induced PC12 cell differentiation model. Results show that NGF treatment causes Golgi enlargement and a parallel increased expression of proteins and mRNAs encoding for proteins required for membrane transport (transport factors). Additionally, a significant increase in CREB3L2 protein and mRNA levels is detected in response to NGF. Both MAPK and cAMP signaling pathways are required for this response. Interestingly, CREB3L2 overexpression hampers the NGF-induced neurite outgrowth while its inhibition enhances the morphological changes driven by NGF. In agreement, CREB3L2 overexpressing cells display higher immunofluorescence intensity of Rab5 GTPase (a negative regulator of PC12 differentiation) than control cells. Also, Rab5 immunofluorescence levels decrease in CREB3L2-depleted cells. Taken together, our findings imply that CREB3L2 is an important downstream effector of NGF-activated pathways, leading to neuronal differentiation.

2 citations

Journal ArticleDOI
01 Apr 2022-Cells
TL;DR: In this paper , the role of CREB3L1 as a TSH-dependent transcriptional regulator of the expression of the sodium/iodide symporter (NIS), a major thyroid protein that mediates iodide uptake, was analyzed.
Abstract: The transcription factor CREB3L1 is expressed in a wide variety of tissues including cartilage, pancreas, and bone. It is located in the endoplasmic reticulum and upon stimulation is transported to the Golgi where is proteolytically cleaved. Then, the N-terminal domain translocates to the nucleus to activate gene expression. In thyroid follicular cells, CREB3L1 is a downstream effector of thyrotropin (TSH), promoting the expression of proteins of the secretory pathway along with an expansion of the Golgi volume. Here, we analyzed the role of CREB3L1 as a TSH-dependent transcriptional regulator of the expression of the sodium/iodide symporter (NIS), a major thyroid protein that mediates iodide uptake. We show that overexpression and inhibition of CREB3L1 induce an increase and decrease in the NIS protein and mRNA levels, respectively. This, in turn, impacts on NIS-mediated iodide uptake. Furthermore, CREB3L1 knockdown hampers the increase the TSH-induced NIS expression levels. Finally, the ability of CREB3L1 to regulate the promoter activity of the NIS-coding gene (Slc5a5) was confirmed. Taken together, our findings highlight the role of CREB3L1 in maintaining the homeostasis of thyroid follicular cells, regulating the adaptation of the secretory pathway as well as the synthesis of thyroid-specific proteins in response to TSH stimulation.

1 citations


Cited by
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Journal ArticleDOI
TL;DR: An overview of the diverse functions of each member of the CREB3 family of transcription factors with special focus on their role in the central nervous system is provided.
Abstract: CREB3 family of transcription factors are ER localized proteins that belong to the bZIP family. They are transported from the ER to the Golgi, cleaved by S1P and S2P proteases and the released N-terminal domains act as transcription factors. CREB3 family members regulate the expression of a large variety of genes and according to their tissue-specific expression profiles they play, among others, roles in acute phase response, lipid metabolism, development, survival, differentiation, organelle autoregulation, and protein secretion. They have been implicated in the ER and Golgi stress responses as regulators of the cell secretory capacity and cell specific cargos. In this review we provide an overview of the diverse functions of each member of the family (CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4) with special focus on their role in the central nervous system.

61 citations

Journal ArticleDOI
TL;DR: The role of AMPK as a central integrating element of cellular pathways with intra- and extra-cellular cues can now be extended to modulation of the anterograde secretory pathway.

35 citations

Journal Article
01 Oct 2017-Nature
TL;DR: In this article, the authors identify the transcription factor CREB3L1 as an essential mediator of PERK's pro-metastatic functions in breast cancer, specifically in the mesenchymal subtype of triple-negative tumors.
Abstract: PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK’s kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would be to target downstream components of the pathway that specifically mediate PERK’s pro-invasive and metastatic functions. Here we identify the transcription factor CREB3L1 as an essential mediator of PERK’s pro-metastatic functions in breast cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype of triple-negative tumors, and its inhibition by genetic or pharmacological methods suppresses cancer cell invasion and metastasis. In patients with this tumor subtype, CREB3L1 expression is predictive of distant metastasis. These findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis and a druggable target for breast cancer therapy.

24 citations

Journal ArticleDOI
TL;DR: Wang et al. as mentioned in this paper performed single-cell RNA sequencing on 144,878 cells from 14 pairs of intrahepatic cholangiocarcinoma (iCCA) tumors and non-tumor liver tissues, and they found that S100P and SPP1 are two markers for iCCA perihilar large duct type and peripheral small duct type.
Abstract: Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCAphl) and peripheral small duct type (iCCApps). S100P + SPP1- iCCAphl has significantly reduced levels of infiltrating CD4+ T cells, CD56+ NK cells, and increased CCL18+ macrophages and PD1+CD8+ T cells compared to S100P-SPP1 + iCCApps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCApps has significantly more SPP1+ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1- iCCAphl. Moreover, S100P-SPP1 + iCCApps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.

23 citations