Protein: Retinoblastoma-like protein homolog lin-35 (Abnormal cell lineage protein 35) (Synthetic multivulva protein lin-35) (G5EDT1)
Organism: Caenorhabditis elegans
Function: Key regulator of cell division which acts as a transcriptional repressor and negatively regulates cell cycle progression in its active unphosphorylated form, but allows cell cycle progression when phosphorylated. When unphosphorylated and in its active form, interacts with E2F transcription factors such as efl-1 to repress their transcriptional activity and negatively regulate the progression through the G1 phase of the cell cycle during postembryonic development. May furthermore act with cell cycle regulator cki-1 to negatively regulate cell cycle progression. Acts redundantly with lin-53, fzr-1 and lin-23 to control cell cycle progression by regulating the expression of G1 phase cyclins. In particular, negatively regulates the expression of the cyclin E homolog cye-1, which is essential for the G1/S phase transition. Regulates cell division in the intestinal lineage, repressing the expression of genes such as cdc-25.2, which are required for intestinal cells to transition from the karyokinesis cell cycle (also known as nuclear division) to endoreplication, a specific growth pathway in the intestinal epithelium required for feeding and gut development in growing larvae during the L1 stage molt. Its role as a transcriptional repressor in the regulation of intestinal cell division during postembryonic development is most likely in complex with an E2F cell cycle regulatory transcription factor efl-1 and its binding partner the synthetic multivulva class B protein dpl-1. Synthetic multivulva (synMuv) class B protein. SynMuv proteins are required to repress the induction of vulval development by Ras signaling and probably act by forming the multiprotein DRM complex that represses transcription. Together with synMuv class B protein lin-53, and redundantly with synMuv class A protein lin-15A, represses transcription to control vulval development, most likely through antagonization of the Ras-signaling pathway in the major hypodermal syncytium hyp7. Acts redundantly with the transcriptional corepressor spr-1 and the zinc finger protein zfp-2 to play a role in vulval morphogenesis, promote germline proliferation and somatic gonad development. Acts redundantly with ubc-18 in the regulation of pharyngeal morphogenesis during embryonic develpment by negatively regulating the expression of proteins such as sup-35. Functions with the SWI/SNF complex and proteins such as pha-1 to regulate larval development. Functions redundantly with xnp-1 to regulate somatic gonad development. Acts redundantly with slr-2 to regulate the expression of intestinal genes required for nutrient utilization. Regulates transcription in response to starvation. Furthermore, in response to starvation, promotes germ cell programmed cell death by negatively regulating the expression of the anti-apoptotic protein ced-9. Conversely, in conjunction with mcd-1, efl-1 and the synthetic multivulva class B proteins dpl-1, lin-37 and lin-52, may also regulate transcription to promote programmed cell death independently of ced-1, ced-8 and ced-9 cell death pathways. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. In particular, negatively regulates the expression of mes-4, a histone methyltransferase that controls the expression of germline specific genes. May play a role in double strand break formation during meiosis. May suppress sensitivity to RNAi. May play a role in the response to endoplasmic reticulum (ER) stress.
Subcellular location: Nucleus {ECO:0000269|PubMed:15621535, ECO:0000269|PubMed:23347407, ECO:0000269|PubMed:25562820, ECO:0000269|PubMed:9875852}. Note=Expressed in dividing cells, but decreased expression after cell cycle exit. {ECO:0000269|PubMed:25562820}.
Interaction partners:
- E2F/DP family winged-helix DNA-binding domain-containing protein
- Transcription factor dpl-1
- Protein lin-9
- Protein lin-52
- G1/S-specific cyclin-D
- Probable histone-binding protein lin-53
- G1/S-specific cyclin-E
- Protein lin-54
- Uncharacterized protein
- Cyclin-dependent kinase 4 homolog
Sequence:
MPKRAADEPGTSTTDPFHEQSPFDAVLAGTETTDTICEEPPAKRIDLDIKQEFNGGVQSGGLIKNESELTQMTIKQETEGNINEARREEEDEEQDEDSRTSMPPALGEDDDYEEDDADSFIDKTNTPPPSQSFLEGCRAANLPNDIVTGAWETYNHAVQRVSLEGSESAWQLSAIYYYLLSKGIKRRGKTIRILIQPFPVSILTIANSFDISVAEMLDKTARFVEIIHSRKIRRYQEYIRRIQEGLAVSCVIFKKFCRIFCKIFEEIKVGSENCPSSHELFTVLWTSFLVMKSRMTVDDLISNYQLLFSILDQVYTEMCSMKEGIVHHLNQKFVEDLLENDCTIIRALCTQFGGSVLDARHFSDHTFKKMEKTGIPSTWNFQEFRDLIMNVPKTAYENYLLQRGSIDERIFIPSVEDFSKIFQSPDTYSVADILKVSYSGRRFRDAEFLTKISNNHCLEKLALGGKVASEKLVTQSKEQPRVPCVEYNLELGNYPDDLESNNQSLYNRLTKIIGSWKLENSKLEEVCGTMSDSPMATILLKSDEMTNKFERTLSAELGETINENIPKYHYNVRKELELVFLIFMEKIIVAELKKKVREEDLLNVIRREEFLDSVFCFCVELILVSNGYDRPFPWSAELCGVHPFMFHKVIDLMITHEKQLSRQMVQHFSRIEETVIEYFSWKSDSPLWPMVVRCPFAHFQEFGEDWADKLNSYSPIKFTPIKKPDDLRDELGRPIVPQNQTSRTLRIFLKRTYFTAARRLQDLTDRVSMGARAKSQCWSLFDYLLRNDTLIFMDRHLDQILLCCVFVIMKINESSMLFTEIMAQYRRQSANSLLVYRSVTVFQEQLNPENPQAVNTKETILERLEGPQKEKTTVDIIKYYNIEFRDRIKYIIGQIDSASDEDLMEMPVATESGLMPVRVYLTHKLSIQTLPKTKHGESKQERAIANLEKSGITIAMERSGD