Open AccessDepletion of the mRNA translation initiation inhibitor, programmed cell death protein 4 (PDCD4), impairs L6 myotube formation
Author(s) -
Maeda Naomi,
Abdullahi Abdikarim,
Beatty Brendan,
Dhanani Zameer,
Adegoke Olasunkanmi A. J.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13395
Subject(s) - translation (biology) , messenger rna , microbiology and biotechnology , programmed cell death , apoptosis , chemistry , biology , biochemistry , gene
The mechanistic (mammalian) target of rapamycin complex 1 ( mTORC 1) signaling is vital for optimal muscle mass and function. Although the significance of mTORC 1 in stimulating muscle growth is unequivocal, evidence in support of its role during muscle regeneration is less clear. Here, we showed that the abundance (protein and mRNA ) of the mTORC 1/S6K1 substrate, programmed cell death protein 4 ( PDCD 4), is upregulated at the onset of differentiation of L6 and C2C12 cells. The increase in PDCD 4 was not associated with any changes in S6K1 activation, but the abundance of beta transducing repeat‐containing protein ( β ‐Tr CP ), the ubiquitin ligase that targets PDCD 4 for degradation, increased. Myoblasts lacking PDCD 4 showed impaired myotube formation and had markedly low levels of MHC ‐1. Analysis of poly ( ADP ‐ribose) Polymerase ( PARP ), caspase 7 and caspase 3 indicated reduced apoptosis in PDCD 4‐deficient cells. Our data demonstrate a role for PDCD 4 in muscle cell formation and suggest that interventions that target this protein may hold promise for managing conditions associated with impaired myotube formation.