We have developed an affinity chromatography method for the isolation of microtubule-associated proteins (MAPs) from soluble cytoplasmic extracts of rat pancreas. Among the ten proteins which copurify with pancreas tubulin on a colchicine derivatives-affinity chromatography, three polypeptides of respectively 58, 55 and 48 kDa strongly bind to the microtubule affinity column. To begin to characterize these proteins, we have generated polyclonal antibodies against tau polypeptides from brains of immature chicken or rat. As judged by immunoblots, the three polypeptides seem to be immunologically related to the tau proteins previously localized in brain.
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J Am Chem Soc
December 2024
Department of Chemical Sciences and Center for Advanced Functional Materials, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur 741246, West Bengal, India.
Triple-negative breast cancer (TNBC) poses significant treatment challenges due to its high metastasis, heterogeneity, and poor biomarker expression. The N-terminus of an octapeptide NAPVSIPQ () was covalently coupled to a carboxylic acid derivative of Ru(2,2'-bipy) () to synthesize an N-stapled short peptide-Rubpy conjugate (). This photosensitizer (PS) was utilized to treat TNBC through microtubule (MT) targeted chemotherapy and photodynamic therapy (PDT).
View Article and Find Full Text PDFJ Biol Chem
December 2024
Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Electronic address:
Microtubule (MT) function plasticity originates from its composition of α- and β-tubulin isotypes and the post-translational modifications of both subunits. Aspects such as MT assembly dynamics, structure, and anticancer drug binding can be modulated by αβ-tubulin heterogeneity. However, the exact molecular mechanism regulating these aspects is only partially understood.
View Article and Find Full Text PDFBioorg Chem
December 2024
School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan. Electronic address:
Septin 9 (SEPT9), a GTPase, known as the fourth cytoskeleton, is widely expressed in various cells and tissues. The functions of SEPT9 are partly similar to other cytoskeletons as a structure protein. Further, SEPT9 can interact with other cytoskeletons, participating in actin dynamics and microtubule regulation.
View Article and Find Full Text PDFAutophagy
December 2024
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, Barcelona, Spain.
MFN1 (mitofusin 1) and MFN2 are key players in mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria juxtaposition, and macroautophagy/autophagy. However, the mechanisms by which these proteins participate in these processes are poorly understood. Here, we studied the interactomes of these two proteins by using CRISPR-Cas9 technology to insert an HA-tag at the C terminus of MFN1 and MFN2, and thus generating HeLa cell lines that endogenously expressed MFN1-HA or MFN2-HA.
View Article and Find Full Text PDFCancer Discov
December 2024
Yale University School of Medicine, New Haven, Connecticut.
In this issue, Klingbeil and colleagues deploy a paralog co-targeting strategy to reveal microtubule affinity-regulating kinases 2 and 3 as redundant negative regulators of the Hippo pathway and potentially actionable targets in YAP/TAZ-addicted tumors. See related article by Klingbeil et.al.
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