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Article

RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner

1
The Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
2
The Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
3
The Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Shinji Miwa
Int. J. Mol. Sci. 2021, 22(10), 5367; https://doi.org/10.3390/ijms22105367
Received: 29 April 2021 / Revised: 14 May 2021 / Accepted: 18 May 2021 / Published: 20 May 2021
(This article belongs to the Special Issue Sarcoma)
Schwann cells are normally quiescent, myelinating glia cells of the peripheral nervous system. Their aberrant proliferation and transformation underlie the development of benign tumors (neurofibromas) as well as deadly malignant peripheral nerve sheath tumors (MPNSTs). We discovered a new driver of MPNSTs, an oncogenic GTPase named RABL6A, that functions in part by inhibiting the RB1 tumor suppressor. RB1 is a key mediator of cellular senescence, a permanent withdrawal from the cell cycle that protects against cell immortalization and transformation. Based on the RABL6A-RB1 link in MPNSTs, we explored the hypothesis that RABL6A promotes Schwann cell proliferation and abrogates their senescence by inhibiting RB1. Using sequentially passaged normal human Schwann cells (NHSCs), we found that the induction of replicative senescence was associated with reduced expression of endogenous RABL6A. Silencing RABL6A in low passage NHSCs caused premature stress-induced senescence, which was largely rescued by co-depletion of RB1. Consistent with those findings, Rabl6-deficient MEFs displayed impaired proliferation and accelerated senescence compared to wildtype MEFs. These results demonstrate that RABL6A is required for maintenance of proper Schwann cell proliferation and imply that aberrantly high RABL6A expression may facilitate malignant transformation. View Full-Text
Keywords: RABL6A; retinoblastoma protein (RB1); Schwann cell; senescence; MPNST RABL6A; retinoblastoma protein (RB1); Schwann cell; senescence; MPNST
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MDPI and ACS Style

Kohlmeyer, J.L.; Kaemmer, C.A.; Umesalma, S.; Gourronc, F.A.; Klingelhutz, A.J.; Quelle, D.E. RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner. Int. J. Mol. Sci. 2021, 22, 5367. https://doi.org/10.3390/ijms22105367

AMA Style

Kohlmeyer JL, Kaemmer CA, Umesalma S, Gourronc FA, Klingelhutz AJ, Quelle DE. RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner. International Journal of Molecular Sciences. 2021; 22(10):5367. https://doi.org/10.3390/ijms22105367

Chicago/Turabian Style

Kohlmeyer, Jordan L., Courtney A. Kaemmer, Shaikamjad Umesalma, Francoise A. Gourronc, Aloysius J. Klingelhutz, and Dawn E. Quelle. 2021. "RABL6A Regulates Schwann Cell Senescence in an RB1-Dependent Manner" International Journal of Molecular Sciences 22, no. 10: 5367. https://doi.org/10.3390/ijms22105367

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