RPS6KA1

Case Study 1: Kazuhiro Katayama, 2016

P-glycoprotein (P-gp) is a critical determinant of multidrug resistance in cancer. This team previously reported that MAPK inhibition downregulates P-gp expression and that P-gp undergoes ubiquitin-proteasomal degradation regulated by UBE2R1 and SCFFbx15. Here, the researchers investigated the crosstalk between MAPK inhibition and the ubiquitin-proteasomal degradation of P-gp. Proteasome inhibitors or knockdown of FBXO15 and/or UBE2R1 cancelled MEK inhibitor-induced P-gp downregulation. RSK1 phosphorylated Thr162 on UBE2R1 but did not phosphorylate FBXO15. MEK and RSK inhibitors increased UBE2R1-WT but not UBE2R1-T162D and -T162A expression. UBE2R1-T162D showed higher self-ubiquitination and destabilisation than UBE2R1-WT and -T162A. Unlike UBE2R1-WT and -T162A, UBE2R1-T162D did not induce P-gp ubiquitination. UBE2R1-WT or -T162A downregulated P-gp expression and upregulated rhodamine 123 level and sensitivity to vincristine and doxorubicin. However, UBE2R1-T162D did not confer any change in P-gp expression, rhodamine 123 accumulation and sensitivity to the drugs.

Fig1. Binding of ERK1 and RSK1 with FBXO15.

Fig2. RSK1-mediated phosphorylation of UBE2R1 in transfectants.

Case Study 2: Amel Salhi, 2015

The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, the researchers tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion.

Fig3. p-RSK1 protein expression in human metastatic melanoma tissues by Western blot analysis.

Fig4. Western blot analysis showing RSK1 levels after transfection with nontargeting.

Fig1. Harmonization of Ca2+, EGF, and oxidative signals. (Tsuyoshi Takata, 2020)

Fig2. Mitogen- and stress-activated kinases (MSKs). (Rana Anjum, 2008)

RPS6KA1 involved in several pathways and played different roles in them. We selected most pathways RPS6KA1 participated on our site, such as MAPK signaling pathway, Oocyte meiosis, mTOR signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with RPS6KA1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

RPS6KA1 has several biochemical functions, for example, ATP binding, cysteine-type endopeptidase inhibitor activity involved in apoptotic process, magnesium ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by RPS6KA1 itself. We selected most functions RPS6KA1 had, and list some proteins which have the same functions with RPS6KA1. You can find most of the proteins on our site.

RPS6KA1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with RPS6KA1 here. Most of them are supplied by our site. Hope this information will be useful for your research of RPS6KA1.

HSP90AB1; VASP; MAPT; CREB1; EIF4B; RPS6; xmd8-92; biotin_acyl-p_probe; YWHAB; ENAH; PPM1G; DDAH2; CFL1; GBP2; TTK; CCT4