Novel retinoblastoma binding protein RBBP9 modulates sex-specific radiation responses in vivo.
Retinoblastoma (RB) tumor suppressor is a key regulator of apoptosis, a central mediator of the proliferative block induced by ionizing radiation (IR) and a binding target for a variety of proteins that regulate its activity. One of the recently discovered and the least investigated of these is the novel Rb-binding protein RBBP9/BOG. We studied the effects of acute and chronic low dose radiation (LDR) exposure on the induction of RBBP9 and RB signaling pathway in vivo in mouse spleen and found that RBBP9 played a pivotal role in IR responses in vivo. We observed that chronic LDR exposure led to a significant increase of RBBP9 expression in males and a significant decrease in females. Elevated RBBP9 expression in males was paralleled by a pronounced dephosphorylation of RB and a significant drop of PCNA and cyclin A expression. On the contrary, chronic exposure in females led to decreased levels of RBBP9 and increased levels of hyperphosphorylated RB (ppRB) in spleen. Decreased levels of ppRB in spleen of chronically exposed males were correlated with strongly elevated apoptotic rates. In females, the radiation-induced increase of apoptotic index was much less pronounced. Quite surprisingly, the observed sex-specific signaling changes did not result in the sex-specificity of cellular proliferation. The molecular mechanisms and possible repercussions of the radiation-induced sex differences in cellular proliferation and apoptosis are discussed.
Cassie
Scott
S
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
Koturbash
Igor
I
Hudson
Darryl
D
Baker
Mike
M
Ilnytskyy
Yaroslav
Y
Rodriguez-Juarez
Rocio
R
Weber
Edgar
E
Kovalchuk
Olga
O
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000502:physiology*; D049109:Cell Proliferation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000502:physiology*; D010766:Phosphorylation; D011832:Radiation Injuries / Q000235:genetics / Q000503:physiopathology*; D011839:Radiation, Ionizing; D016160:Retinoblastoma Protein / Q000378:metabolism; D057057:Serine Proteases; D012737:Sex Factors; D015398:Signal Transduction; D013154:Spleen / Q000502:physiology
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; C485186:Rbbp9 protein, mouse; D057057:Serine Proteases