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lin-35

Gene
lin-35
Protein
Retinoblastoma-like protein homolog lin-35
Organism
Caenorhabditis elegans
Length
961 amino acids
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 (PubMed:11684669, PubMed:12062054, PubMed:16287966, PubMed:17466069, PubMed:25562820). 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 (PubMed:11684669, PubMed:12062054, PubMed:15238519, PubMed:17466069, PubMed:25562820). May furthermore act with cell cycle regulator cki-1 to negatively regulate cell cycle progression (PubMed:11684669). Acts redundantly with lin-53, fzr-1 and lin-23 to control cell cycle progression by regulating the expression of G1 phase cyclins (PubMed:11850412, PubMed:25562820). In particular, negatively regulates the expression of the cyclin E homolog cye-1, which is essential for the G1/S phase transition (PubMed:16287966, PubMed:17466069). 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 (PubMed:17466069, PubMed:27104746). 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 (PubMed:17466069). Synthetic multivulva (synMuv) class B protein (PubMed:9875852, PubMed:11850412). 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 (PubMed:9875852, PubMed:17075059). 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 (PubMed:9875852, PubMed:15621535, PubMed:16624904, PubMed:26100681). 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 (PubMed:17417969, PubMed:17070797). 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 (PubMed:12783801, PubMed:19521497, PubMed:24214340). Functions with the SWI/SNF complex and proteins such as pha-1 to regulate larval development (PubMed:15196946, PubMed:15280233). Functions redundantly with xnp-1 to regulate somatic gonad development (PubMed:15328017, PubMed:15649460). Acts redundantly with slr-2 to regulate the expression of intestinal genes required for nutrient utilization (PubMed:18437219, PubMed:22542970). Regulates transcription in response to starvation (PubMed:23664972). Furthermore, in response to starvation, promotes germ cell programmed cell death by negatively regulating the expression of the anti-apoptotic protein ced-9 (PubMed:17881492, PubMed:24752899). 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 (PubMed:17237514). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (PubMed:23347407). In particular, negatively regulates the expression of mes-4, a histone methyltransferase that controls the expression of germline specific genes (PubMed:23347407). May play a role in double strand break formation during meiosis (PubMed:15315757). May suppress sensitivity to RNAi (PubMed:16507136, PubMed:17417969). May play a role in the response to endoplasmic reticulum (ER) stress (PubMed:24715729).
Similarity
Belongs to the retinoblastoma protein (RB) family.
Mass
110.903 kDa
Sequence
MPKRAADEPGTSTTDPFHEQSPFDAVLAGTETTDTICEEPPAKRIDLDIKQEFNGGVQSGGLIKNESELTQMTIKQETEGNINEARREEEDEEQDEDSRTSMPPALGEDDDYEEDDADSFIDKTNTPPPSQSFLEGCRAANLPNDIVTGAWETYNHAVQRVSLEGSESAWQLSAIYYYLLSKGIKRRGKTIRILIQPFPVSILTIANSFDISVAEMLDKTARFVEIIHSRKIRRYQEYIRRIQEGLAVSCVIFKKFCRIFCKIFEEIKVGSENCPSSHELFTVLWTSFLVMKSRMTVDDLISNYQLLFSILDQVYTEMCSMKEGIVHHLNQKFVEDLLENDCTIIRALCTQFGGSVLDARHFSDHTFKKMEKTGIPSTWNFQEFRDLIMNVPKTAYENYLLQRGSIDERIFIPSVEDFSKIFQSPDTYSVADILKVSYSGRRFRDAEFLTKISNNHCLEKLALGGKVASEKLVTQSKEQPRVPCVEYNLELGNYPDDLESNNQSLYNRLTKIIGSWKLENSKLEEVCGTMSDSPMATILLKSDEMTNKFERTLSAELGETINENIPKYHYNVRKELELVFLIFMEKIIVAELKKKVREEDLLNVIRREEFLDSVFCFCVELILVSNGYDRPFPWSAELCGVHPFMFHKVIDLMITHEKQLSRQMVQHFSRIEETVIEYFSWKSDSPLWPMVVRCPFAHFQEFGEDWADKLNSYSPIKFTPIKKPDDLRDELGRPIVPQNQTSRTLRIFLKRTYFTAARRLQDLTDRVSMGARAKSQCWSLFDYLLRNDTLIFMDRHLDQILLCCVFVIMKINESSMLFTEIMAQYRRQSANSLLVYRSVTVFQEQLNPENPQAVNTKETILERLEGPQKEKTTVDIIKYYNIEFRDRIKYIIGQIDSASDEDLMEMPVATESGLMPVRVYLTHKLSIQTLPKTKHGESKQERAIANLEKSGITIAMERSGD