Inhibition of cell death by ribosomal protein L35a.
In order to better understand how tumor cells develop resistance to chemotherapy drugs, we screened a human cDNA expression library in Jurkat cells for cDNA's that conferred resistance to doxorubicin-induced cell death. One of the cDNA's isolated in the screen codes for ribosomal protein L35a, a component of the large subunit of the ribosome. Jurkat cells engineered to overexpress L35a protein were more resistant not only to doxorubicin but also to UV-irradiation, anti-Fas antibody, and serum starvation compared to Jurkat cells expressing endogenous levels of L35a. Jurkat cells overexpressing L35a did not have increased levels of the anti-apoptotic proteins Bcl-2 or Bcl-xL, the drug efflux pump P-glycoprotein, nor altered cellular growth kinetics or total protein synthesis. Our results provide new insight into L35a function and suggest that it may have a role in the cellular response to cytotoxic damage. Since L35a RNA is overexpressed in a significant number of glioblastoma multiforme (GBM) brain tumors, our results may stimulate further investigation into the possible role of L35a in the resistance of GBM to cytotoxic therapy.
Lopez
Charles D
CD
Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, MC L586, Portland, OR 97201-3098, USA. lopezc@ohsu.edu
Martinovsky
Gary
G
Naumovski
Louie
L
D016923:Cell Death; D002455:Cell Division; D018076:DNA, Complementary / Q000302:isolation & purification; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D014176:Protein Biosynthesis; D012269:Ribosomal Proteins / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; C489281:RPL35A protein, human; D012269:Ribosomal Proteins