تقرير
SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia
| العنوان: | SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia |
|---|---|
| المؤلفون: | Polyanskaya, Sofya A, Moreno, Rosamaria Y, Lu, Bin, Feng, Ruopeng, Yao, Yu, Irani, Seema, Klingbeil, Olaf, Yang, Zhaolin, Wei, Yiliang, Demerdash, Osama E, Benjamin, Lukas A, Weiss, Mitchell J, Zhang, Yan Jessie, Vakoc, Christopher R |
| سنة النشر: | 2022 |
| المجموعة: | Cold Spring Harbor Laboratory: CSHL Institutional Repository |
| مصطلحات موضوعية: | bioinformatics, cancer, diseases & disorders, genetics & nucleic acid processing, genomics and proteomics, Investigative techniques and equipment, protein structure, function, modification, acute myeloid leukemia, cell functions, cell line, cell proliferation, cell types, cell types and functions, CRISPR-Cas9, enzymes, leukemia, organs, tissues, organelles, phosphorylation, protein expression, protein phosphatase, protein types, signal transduction, tissues types and functions, cancer types |
| الوصف: | Acute myeloid leukemia (AML) cells rely on phospho-signaling pathways to gain unlimited proliferation potential. Here, we use domain-focused CRISPR screening and identify the nuclear phosphatase SCP4 as a dependency in AML, yet this enzyme is dispensable in normal hematopoietic progenitor cells. Using CRISPR exon scanning and gene complementation assays, we show that the catalytic function of SCP4 is essential in AML. Through mass spectrometry analysis of affinity-purified complexes, we identify the kinase paralogs STK35 and PDIK1L as binding partners and substrates of the SCP4 phosphatase domain. We show that STK35 and PDIK1L function catalytically and redundantly in the same pathway as SCP4 to maintain AML proliferation and to support amino acid biosynthesis and transport. We provide evidence that SCP4 regulates STK35/PDIK1L through two distinct mechanisms: catalytic removal of inhibitory phosphorylation and by promoting kinase stability. Our findings reveal a phosphatase-kinase signaling complex that supports the pathogenesis of AML. |
| نوع الوثيقة: | report |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://repository.cshl.edu/id/eprint/40491/1/2022.Polyanskaya.SCP4_STK35.pdfTest; Polyanskaya, Sofya A, Moreno, Rosamaria Y, Lu, Bin, Feng, Ruopeng, Yao, Yu, Irani, Seema, Klingbeil, Olaf, Yang, Zhaolin, Wei, Yiliang, Demerdash, Osama E, Benjamin, Lukas A, Weiss, Mitchell J, Zhang, Yan Jessie, Vakoc, Christopher R (January 2022) SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia. Cell Reports, 38 (2). p. 110233. ISSN 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.110233 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2021.110233Test https://repository.cshl.edu/id/eprint/40491Test/ https://repository.cshl.edu/id/eprint/40491/1/2022.Polyanskaya.SCP4_STK35.pdfTest https://www.ncbi.nlm.nih.gov/pubmed/35021089Test |
| حقوق: | cc_by_nc_nd |
| رقم الانضمام: | edsbas.1D24298C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2021.110233 |
|---|