LIN-35 is the only C. elegans representative of the pocket protein family, which includes the mammalian Retinoblastoma protein pRB and its paralogs
p107 and
p130. This family of proteins plays keys roles in cell cycle regulation, apoptosis, development, and stress among several others. The Conradt lab showed in 2007 that LIN-35/RB partially suppresses germ cells physiological apoptosis by repressing
ced-9 expression, an anti-apoptotic gene homologue to the human proto-oncogene BCL2. Later, in 2014, our laboratory showed that LIN-35/Rb is also required to induce germ cell apoptosis during starvation. We observed that after 6h of bacteria deprivation,
lin-35/Rb expression increases considerably, and we are trying to gain a greater understanding on the mechanism that regulates
lin-35/Rb in this condition. Using ModEncode database, we looked for transcription factors that presumably bind to the putative promoter region of
lin-35/Rb. We are testing if those transcription factors could be involved in
lin-35/Rb regulation during starvation-induce apoptosis. Furthermore we are generating a
lin-35p:gfp reporter to test the influence of these transcription factors on this promoter. By bioinformatics, we found that the transcription factors SKN-1, ATF-7, SP-1/SPTF-3 and NHR-28 might directly or indirectly bind to the putative
lin-35 promoter. By RNAi, we observed that
skn-1 and
atf-7 are not required for starvation-induced apoptosis therefore we do not think they might regulate
lin-35 under starvation conditions to induce apoptosis. In contrast,
sptf-3/SP-1 and
nhr-28 are required to induce germ cell apoptosis during starvation. Furthermore by qPCR, we observed that
lin-35/Rb expression is down regulated in mutants strains for these activators; suggesting that these regulators might be controlling
lin-35/Rb expression during starvation to trigger germ cell apoptosis. We will continue studying if SP-1/SPTF-3 and NHR-28 are indeed required to regulate
lin-35 expression under stress. Our research is supported by grants 220987 (CONACyT) and IN208918 (PAPIIT-UNAM).