RPS6KA4: A Potential Drug Target and Biomarker for Nuclear Mitogen- and Stress-Activated Protein Kinase 2

Target Name: RPS6KA4

NCBI ID: G8986

RPS6KA4: A Potential Drug Target and Biomarker for Nuclear Mitogen- and Stress-Activated Protein Kinase 2

Nuclear mitogen- and stress-activated protein kinase 2 (RPS6KA4) is a key regulator of cellular responses to mechanical, chemical, and biological stress, thereby ensuring the survival and integrity of cells under various conditions. RPS6KA4 is a nuclear protein that belongs to the Mitogen-Activated Protein Kinase (MAPK) family 6A (MAPK6A) and has been implicated in various cellular processes, including cell survival, proliferation, migration, and angiogenesis.

The RPS6KA4 gene has four isoforms, two of which are nuclear and two of which are cytoplasmic. The nuclear isoform is predominantly expressed in the nuclei, while the cytoplasmic isoform is mainly distributed in the cytoplasm. The nuclear isoform is responsible for regulating the MAPK6A signaling pathway, which involves the formation of a protein complex between the MAPK6A kinase and the transcription factor p21.

During cellular stress, RPS6KA4 is activated and translates into a nuclear protein with a Mr of approximately 25 kDa, which is known as RPS6KA4-N. The RPS6KA4-N protein plays a crucial role in regulating cellular responses to stress, as it interacts with various cellular components, including the transcription factor, activator protein 1 (AP-1), and the stress-associated protein Sap-1.

Several studies have demonstrated that RPS6KA4 is involved in various cellular processes, including cell growth, apoptosis, and cell-cell fusion. For example, overexpression of RPS6KA4 has been shown to promote the growth of cancer cells and to inhibit the cell cycle. Additionally, RPS6KA4 has been implicated in the regulation of cell migration and the assembly of microtubules.

Furthermore, RPS6KA4 has also been implicated in the regulation of cellular stress responses, including the transition from a state of stress to a state of recovery. For instance, RPS6KA4 has been shown to play a role in the regulation of DNA damage repair and cell survival after exposure to ionizing radiation.

In addition to its role in cellular stress responses, RPS6KA4 has also been shown to be involved in the regulation of cellular signaling pathways, including the TGF-灏? pathway. For example, RPS6KA4 has been shown to interact with the transcription factor, SMAD1, and to regulate the translation of the transcription factor, p21.

Given the significant involvement of RPS6KA4 in various cellular processes, it is a potential drug target and biomarker for various diseases. The identification of small molecules that can specifically modulate RPS6KA4 activity may provide new insights into the regulation of cellular processes and the development of new therapeutic strategies.

Conclusion

In conclusion, RPS6KA4 is a key regulator of cellular responses to mechanical, chemical, and biological stress and has been implicated in various cellular processes, including cell survival, proliferation, migration, and angiogenesis. The nuclear isoform of RPS6KA4 is predominantly expressed in the nuclei and plays a crucial role in regulating the MAPK6A signaling pathway. The identification of small molecules that can specifically modulate RPS6KA4 activity may provide new insights into the regulation of cellular processes and the development of new therapeutic strategies.

Protein Name: Ribosomal Protein S6 Kinase A4

Functions: Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors

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